Clinical Endocrinology News

It took less than a day for physician groups to start pushing back at the Centers for Medicare & Medicaid Services over its new Medicaid block grant plan, which was introduced on Jan. 30.

Dubbed “Healthy Adult Opportunity,” the agency is offering all states the chance to participate in a block grant program through the 1115 waiver process.

According to a fact sheet issued by the agency, the program will focus on “adults under age 65 who are not eligible for Medicaid on the basis of disability or their need for long term care services and supports, and who are not eligible under a state plan. Other very low-income parents, children, pregnant women, elderly adults, and people eligible on the basis of a disability will not be directly affected – except from the improvement that results from states reinvesting savings into strengthening their overall programs.”

States will be operating within a defined budget when participating in the program and expenditures exceeding that defined budget will not be eligible for additional federal funding. Budgets will be based on a state’s historic costs, as well as national and regional trends, and will be tied to inflation with the potential to have adjustments made for extraordinary events. States can set their baseline using the prior year’s total spending or a per-enrollee spending model.

A Jan. 30 letter to state Medicaid directors notes that states participating in the program “will be granted extensive flexibility to test alternative approaches to implementing their Medicaid programs, including the ability to make many ongoing program adjustments without the need for demonstration or state plan amendments that require prior approval.”

Among the activities states can engage in under this plan are adjusting cost-sharing requirements, adopting a closed formulary, and applying additional conditions of eligibility. Requests, if approved, will be approved for a 5-year initial period, with a renewal option of up to 10 years.

But physician groups are not seeing a benefit with this new block grant program.

“Moving to a block grant system will likely limit the ability of Medicaid patients to receive preventive and needed medical care from their family physicians, and it will only increase the health disparities that exist in these communities, worsen overall health outcomes, and ultimately increase costs,” Gary LeRoy, MD, president of the American Academy of Family Physicians, said in a statement.

The American Medical Association concurred.

“The AMA opposes caps on federal Medicaid funding, such as block grants, because they would increase the number of uninsured and undermine Medicaid’s role as an indispensable safety net,” Patrice Harris, MD, the AMA’s president, said in a statement. “The AMA supports flexibility in Medicaid and encourages CMS to work with states to develop and test new Medicaid models that best meet the needs and priorities of low-income patients. While encouraging flexibility, the AMA is mindful that expanding Medicaid has been a literal lifesaver for low-income patients. We need to find ways to build on this success. We look forward to reviewing the proposal in detail.”

Officials at the American College of Obstetricians and Gynecologists said the changes have the potential to harm women and children’s health, as well as negatively impact physician reimbursement and ultimately access to care.

“Limits on the federal contribution to the Medicaid program would negatively impact patients by forcing states to reduce the number of people who are eligible for Medicaid coverage, eliminate covered services, and increase beneficiary cost-sharing,” ACOG President Ted Anderson, MD, said in a statement. “ACOG is also concerned that this block grant opportunity could lower physician reimbursement for certain services, forcing providers out of the program and jeopardizing patients’ ability to access health care services. Given our nation’s stark rates of maternal mortality and severe maternal morbidity, we are alarmed by the Administration’s willingness to weaken physician payment in Medicaid.”

gtwachtman@mdedge.com

It took less than a day for physician groups to start pushing back at the Centers for Medicare & Medicaid Services over its new Medicaid block grant plan, which was introduced on Jan. 30.

Dubbed “Healthy Adult Opportunity,” the agency is offering all states the chance to participate in a block grant program through the 1115 waiver process.

According to a fact sheet issued by the agency, the program will focus on “adults under age 65 who are not eligible for Medicaid on the basis of disability or their need for long term care services and supports, and who are not eligible under a state plan. Other very low-income parents, children, pregnant women, elderly adults, and people eligible on the basis of a disability will not be directly affected – except from the improvement that results from states reinvesting savings into strengthening their overall programs.”

States will be operating within a defined budget when participating in the program and expenditures exceeding that defined budget will not be eligible for additional federal funding. Budgets will be based on a state’s historic costs, as well as national and regional trends, and will be tied to inflation with the potential to have adjustments made for extraordinary events. States can set their baseline using the prior year’s total spending or a per-enrollee spending model.

A Jan. 30 letter to state Medicaid directors notes that states participating in the program “will be granted extensive flexibility to test alternative approaches to implementing their Medicaid programs, including the ability to make many ongoing program adjustments without the need for demonstration or state plan amendments that require prior approval.”

Among the activities states can engage in under this plan are adjusting cost-sharing requirements, adopting a closed formulary, and applying additional conditions of eligibility. Requests, if approved, will be approved for a 5-year initial period, with a renewal option of up to 10 years.

But physician groups are not seeing a benefit with this new block grant program.

“Moving to a block grant system will likely limit the ability of Medicaid patients to receive preventive and needed medical care from their family physicians, and it will only increase the health disparities that exist in these communities, worsen overall health outcomes, and ultimately increase costs,” Gary LeRoy, MD, president of the American Academy of Family Physicians, said in a statement.

The American Medical Association concurred.

“The AMA opposes caps on federal Medicaid funding, such as block grants, because they would increase the number of uninsured and undermine Medicaid’s role as an indispensable safety net,” Patrice Harris, MD, the AMA’s president, said in a statement. “The AMA supports flexibility in Medicaid and encourages CMS to work with states to develop and test new Medicaid models that best meet the needs and priorities of low-income patients. While encouraging flexibility, the AMA is mindful that expanding Medicaid has been a literal lifesaver for low-income patients. We need to find ways to build on this success. We look forward to reviewing the proposal in detail.”

Officials at the American College of Obstetricians and Gynecologists said the changes have the potential to harm women and children’s health, as well as negatively impact physician reimbursement and ultimately access to care.

“Limits on the federal contribution to the Medicaid program would negatively impact patients by forcing states to reduce the number of people who are eligible for Medicaid coverage, eliminate covered services, and increase beneficiary cost-sharing,” ACOG President Ted Anderson, MD, said in a statement. “ACOG is also concerned that this block grant opportunity could lower physician reimbursement for certain services, forcing providers out of the program and jeopardizing patients’ ability to access health care services. Given our nation’s stark rates of maternal mortality and severe maternal morbidity, we are alarmed by the Administration’s willingness to weaken physician payment in Medicaid.”

gtwachtman@mdedge.com

It took less than a day for physician groups to start pushing back at the Centers for Medicare & Medicaid Services over its new Medicaid block grant plan, which was introduced on Jan. 30.

Dubbed “Healthy Adult Opportunity,” the agency is offering all states the chance to participate in a block grant program through the 1115 waiver process.

According to a fact sheet issued by the agency, the program will focus on “adults under age 65 who are not eligible for Medicaid on the basis of disability or their need for long term care services and supports, and who are not eligible under a state plan. Other very low-income parents, children, pregnant women, elderly adults, and people eligible on the basis of a disability will not be directly affected – except from the improvement that results from states reinvesting savings into strengthening their overall programs.”

States will be operating within a defined budget when participating in the program and expenditures exceeding that defined budget will not be eligible for additional federal funding. Budgets will be based on a state’s historic costs, as well as national and regional trends, and will be tied to inflation with the potential to have adjustments made for extraordinary events. States can set their baseline using the prior year’s total spending or a per-enrollee spending model.

A Jan. 30 letter to state Medicaid directors notes that states participating in the program “will be granted extensive flexibility to test alternative approaches to implementing their Medicaid programs, including the ability to make many ongoing program adjustments without the need for demonstration or state plan amendments that require prior approval.”

Among the activities states can engage in under this plan are adjusting cost-sharing requirements, adopting a closed formulary, and applying additional conditions of eligibility. Requests, if approved, will be approved for a 5-year initial period, with a renewal option of up to 10 years.

But physician groups are not seeing a benefit with this new block grant program.

“Moving to a block grant system will likely limit the ability of Medicaid patients to receive preventive and needed medical care from their family physicians, and it will only increase the health disparities that exist in these communities, worsen overall health outcomes, and ultimately increase costs,” Gary LeRoy, MD, president of the American Academy of Family Physicians, said in a statement.

The American Medical Association concurred.

“The AMA opposes caps on federal Medicaid funding, such as block grants, because they would increase the number of uninsured and undermine Medicaid’s role as an indispensable safety net,” Patrice Harris, MD, the AMA’s president, said in a statement. “The AMA supports flexibility in Medicaid and encourages CMS to work with states to develop and test new Medicaid models that best meet the needs and priorities of low-income patients. While encouraging flexibility, the AMA is mindful that expanding Medicaid has been a literal lifesaver for low-income patients. We need to find ways to build on this success. We look forward to reviewing the proposal in detail.”

Officials at the American College of Obstetricians and Gynecologists said the changes have the potential to harm women and children’s health, as well as negatively impact physician reimbursement and ultimately access to care.

“Limits on the federal contribution to the Medicaid program would negatively impact patients by forcing states to reduce the number of people who are eligible for Medicaid coverage, eliminate covered services, and increase beneficiary cost-sharing,” ACOG President Ted Anderson, MD, said in a statement. “ACOG is also concerned that this block grant opportunity could lower physician reimbursement for certain services, forcing providers out of the program and jeopardizing patients’ ability to access health care services. Given our nation’s stark rates of maternal mortality and severe maternal morbidity, we are alarmed by the Administration’s willingness to weaken physician payment in Medicaid.”

gtwachtman@mdedge.com

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

LOS ANGELES – Injections may be the most common way for patients with diabetes to take insulin, but other modes of delivery are coming of age.

Doug Brunk/MDedge News

George Grunberger, MD, chairman of the Grunberger Diabetes Institute in Bloomfield Township, Mich., said that at least seven different agents that are being studied for the oral delivery of biologics for diabetes.

He outlined several at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
 

Oral insulin

ORMD-0801 from Oramed is an oral insulin capsule that prevents enzyme degradation and enhances intestinal absorption. Top-line, unpublished findings from a phase 2 study, which the company announced in November 2019, showed that ORMD-0801 significantly reduced hemoglobin A_1c levels in patients with type 2 diabetes who were inadequately controlled on other standard-of-care drugs. ORMD-0801 dosed once daily reduced HbA_1c by 0.60%, compared with 0.06% by placebo. “We’ll see when it’s going to wind up in the clinic,” Dr. Grunberger said. Oramed is also developing an oral glucagonlike peptide–1 analogue capsule, ORMD-0901, which has potential to be the first orally ingestible GLP-1 analogue.

Inhaled and absorbed insulin

Technosphere insulin (Affreza) is a novel inhalation powder for the treatment of diabetes that was developed by MannKind and approved by the Food and Drug Administration in 2014. Clinical studies have shown that Technosphere insulin delivers insulin with an ultrarapid pharmacokinetic profile that is different from all other insulin products, but similar to natural insulin release. “The idea was to develop a more patient-friendly device to deliver insulin directly into the lungs,” said Dr. Grunberger, who is also a clinical professor of internal medicine and molecular medicine and genetics at Wayne State University, Detroit. “When you inhale this into the lungs, there is one cell layer between the air sac and the circulation, so it works very quickly. The idea is to try to avoid injecting insulin to see if it helps. This is a prandial insulin – you inhale it before meals. The whole idea is that hopefully, you can reduce any fear of delayed postprandial hyperglycemia.”

In a randomized trial of 353 patients with inadequately controlled type 2 diabetes, those in the Technosphere insulin arm significantly reduced HbA_1c by 0.8% from a baseline of 8.3%, compared with the placebo arm, which was reduced by 0.4% (P less than .0001; Diabetes Care. 2015;38[12]:2274-81). A greater number of patients treated with Technosphere insulin achieved an HbA_1c of 7.0% or less, compared with placebo (38% vs. 19%; P = .0005). Dr. Grunberger noted that, in clinical trials lasting up to 2 years, patients treated with Technosphere insulin had a 40-mL greater decline from baseline in forced expiratory volume in 1 second (FEV₁ ), compared with patients treated with comparator antidiabetes treatments. “But once you stop using the drug, FEV₁ reverts to normal,” he said. “So, there does not appear to be lasting damage to your lungs and respiratory ability.”

In another development, Oral-Lyn from Generex Biotechnology, which delivers insulin through the oral mucosa, is being evaluated as a potential treatment option. In 2015, Generex partnered with the University of Toronto’s Center for Molecular Design and Preformulations to increase the bioavailability of insulin in the product and to reduce the number of sprays required to achieve effective prandial glucose control. In 2019, the company formed the NuGenerex Diabetes Research Center, which intended to accelerate the development of the reformulated Oral-Lyn-2, for type 2 diabetes, and Altsulin, for the treatment of type 1 diabetes. The programs are expected to initiate in the first quarter of 2020.

In the meantime, studies of intranasally delivered insulin continue to advance. “It works. It lowers glucose, but there is a whole slew of knowledge now about how it can also improve neurocognitive function,” Dr. Grunberger said.
 

Oral GLP-1 receptor agonists

Oral versions of glucagonlike peptide–1 (GLP-1) receptor agonists are also emerging as a treatment option. The FDA recently approved the first oral GLP-1 receptor agonist, semaglutide bound in the absorption enhancer sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). According to data from manufacturer Novo Nordisk, SNAC facilitates local increase of pH, which leads to a higher solubility. SNAC interacts with cell membranes of gastric mucosa, facilitating absorption within 30 minutes, “so the drug can penetrate the mucosa without lasting damage,” Dr. Grunberger said. The SNAC effect is size dependent and fully reversible.

In PIONEER 3, researchers found that, in adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide at dosages of 7 and 14 mg/day resulted in significantly greater reductions in HbA_1c over 26 weeks, compared with sitagliptin, but there was no significant benefit with the 3-mg/d dosage (JAMA. 2019;321[15]:1466-80). In PIONEER 4, researchers compared the efficacy and safety of oral semaglutide with subcutaneous liraglutide (Lancet. 2019;394[10192]:P39-50). “There was no difference in HbA_1c effect between the two groups, but oral semaglutide beat out sitagliptin in terms of weight loss,” Dr. Grunberger said. “It’s going to be interesting to see what’s going to happen in the marketplace as the drug gets widely launched.”
 

Nasal glucagon

He closed out his presentation by discussing the July 2019 FDA approval of Eli Lilly’s nasal glucagon for severe hypoglycemia – the first such treatment that can be administered without an injection. The nasally administered dry powder, known as Baqsimi, is a welcome alternative to current glucagon kits, “which contain multiple components,” said Dr. Grunberger, who is also a past president of the American Association of Clinical Endocrinologists. An adult pivotal study showed that supraphysiologic levels of glucagon were achieved within 5 minutes with both nasal and intramuscular glucagon (Diabetes Care. 2016;39[2]:264-70). Headache and nasal symptoms occurred more frequently with nasal glucagon, but most were resolved within 1 day. In addition, nausea and vomiting occurred at similar frequencies with nasal and intramuscular glucacon, and most cases were resolved within 1 day.

Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years, (Diabetes Care. 2016;39[4]:555-62).

Dr. Grunberger disclosed that has research contracts with Medtronic and Eli Lilly, and that he serves on speakers bureaus of Eli Lilly, Janssen, Novo Nordisk, and Sanofi.

dbrunk@mdedge.com

Diabetes is a complex disease with a range of nuanced therapy options and a plethora of risk factors that could significantly affect patient quality of life and long-term outcomes. From the outset, after diagnosis, a selected regimen has to be meticulously tailored to a patient’s clinical needs and monitored over time, and many other nonclinical variables, such as patient preference, social history, access to care, and support systems, as well as the cost of the drugs and its impact on the patient, must also be considered.

The increase in the incidence of youth-onset diabetes means that more young adults are making the transition from pediatric to adult care, and careful care coordination is paramount at the handover point to ensure that a full and complete account of the history gets transferred to the adult-care provider.

So how do you distill the information from all those records (on paper and online) that you’ve accumulated during the time you’ve been treating a young adult who is now transitioning to adult care?
 

Transition summary

One resource that can facilitate this handover is the transition summary. It effectively consolidates and packages the aforementioned aspects of care and patient history so that the adult-care provider does not have to collect the patient’s history from the start. The transition summary should not be confused with the discharge or medical summary, which focuses only on the preceding clinical care.

It is important to stress at this stage that collaboration between the pediatric- and adult-care providers is crucial to the success of such a summary, from its creation, to its implementation, and through the subsequent and inevitable revisions and updates.
 

Benefits all around

After we introduced the transition summary at my institution, we found that the average initial patient visit with the new adult-care provider decreased by 12 minutes (with a range of 6-19 min). The adult-care providers welcomed receiving such detailed, important patient information packaged in a concise and readily accessible format. It helped them identify the preceding care team members, which facilitated continuity of care, and it also helped them forge a better therapeutic relationship with the patient earlier on in their engagement.

We also learned that patients were more comfortable with the transition, and the referring providers were relieved and reassured that their patients would continue to receive personalized care with the new adult-care provider.

At a personal level, I found I was less stressed as I could spend better-quality clinical time with patients. And I got to eliminate those unwieldy stacks of medical records since getting buy-in from divisional and IT leadership enabled us to automate the entire process of information transfer.

It is important to note that the patient has to consent to release of medical records to other institutions.
 

Setting up the summary

At our clinic, I started out by adapting the transition summary from guidelines provided by the Endocrine Society to make a template. Then, in collaboration with my pediatric colleagues, I removed and added information so that the revised document would contain information that is vitally important and not readily available in the chart and would be feasible to fill out. For example, we included details such as the patient’s psychosocial history, an estimation of the patient barriers to diabetes management, family relationship issues, and the patient’s reasons for not adopting advanced diabetes technology (see accompanying example of a transition summary) .

I kept the summary brief, at two pages, and piloted it with referring providers who were interested in using the summary and with related supporting services. I also sought buy-in from my institution. This meant that I needed pediatric and adult divisional leadership support, which offered me information technology, resources, and expertise to automate the summary within the electronic health record. Once I had feedback from would-be users, we revised and updated the summary. We set up training for staff, including pediatric providers, nurse practitioners, social workers, and nurses who could fill out the summary, and ultimately succeeded in making it mandatory that the adult-care provider receive a summary before scheduling or seeing the transfer patient.

I started out with a paper version, and once we’d refined the questions, we incorporated it into the electronic medical record.

The information we use in our summary is grouped under the following headings:

• Reason for transition.
• Diabetes type.
• Degree of diabetes control.
• Type of insulin therapy and supplies.
• Current and former insulin regimen: reasons for discontinuation of any therapies or reluctance to start any therapies.
• Diabetes health maintenance.
• Social history and support, including living situation, main social support network, child protective services involvement.
• Other pertinent medical surgical history, including psychiatric disease.

Tips and takeaways

Top of the list of takeaways is that you should make the final document work for you, your colleagues, and ultimately, your patients – customize it as you see fit, but be sure to keep it short and easy to fill out. Make a note as you start using it in practice of what you think might be missing from the chart and whether updates are needed. If you can, it’s a great idea to fold the transfer summary into the electronic medical record, though it’s not imperative. Care coordination is key to successful transfer of patients, whether from pediatric to adult care or hospital to home. A small change to work flow can result in a huge change in patient and provider satisfaction, as well as a reduction in visit times.
 

Dr. Agarwal is director of the Supporting Emerging Adults With Diabetes (SEAD) program at Montefiore Medical Center and assistant professor of medicine at Albert Einstein College of Medicine, New York. She reports no disclosures or financial conflicts of interest. Write to her at cenews@mdedge.com.

Diabetes is a complex disease with a range of nuanced therapy options and a plethora of risk factors that could significantly affect patient quality of life and long-term outcomes. From the outset, after diagnosis, a selected regimen has to be meticulously tailored to a patient’s clinical needs and monitored over time, and many other nonclinical variables, such as patient preference, social history, access to care, and support systems, as well as the cost of the drugs and its impact on the patient, must also be considered.

The increase in the incidence of youth-onset diabetes means that more young adults are making the transition from pediatric to adult care, and careful care coordination is paramount at the handover point to ensure that a full and complete account of the history gets transferred to the adult-care provider.

So how do you distill the information from all those records (on paper and online) that you’ve accumulated during the time you’ve been treating a young adult who is now transitioning to adult care?
 

Transition summary

One resource that can facilitate this handover is the transition summary. It effectively consolidates and packages the aforementioned aspects of care and patient history so that the adult-care provider does not have to collect the patient’s history from the start. The transition summary should not be confused with the discharge or medical summary, which focuses only on the preceding clinical care.

It is important to stress at this stage that collaboration between the pediatric- and adult-care providers is crucial to the success of such a summary, from its creation, to its implementation, and through the subsequent and inevitable revisions and updates.
 

Benefits all around

After we introduced the transition summary at my institution, we found that the average initial patient visit with the new adult-care provider decreased by 12 minutes (with a range of 6-19 min). The adult-care providers welcomed receiving such detailed, important patient information packaged in a concise and readily accessible format. It helped them identify the preceding care team members, which facilitated continuity of care, and it also helped them forge a better therapeutic relationship with the patient earlier on in their engagement.

We also learned that patients were more comfortable with the transition, and the referring providers were relieved and reassured that their patients would continue to receive personalized care with the new adult-care provider.

At a personal level, I found I was less stressed as I could spend better-quality clinical time with patients. And I got to eliminate those unwieldy stacks of medical records since getting buy-in from divisional and IT leadership enabled us to automate the entire process of information transfer.

It is important to note that the patient has to consent to release of medical records to other institutions.
 

Setting up the summary

At our clinic, I started out by adapting the transition summary from guidelines provided by the Endocrine Society to make a template. Then, in collaboration with my pediatric colleagues, I removed and added information so that the revised document would contain information that is vitally important and not readily available in the chart and would be feasible to fill out. For example, we included details such as the patient’s psychosocial history, an estimation of the patient barriers to diabetes management, family relationship issues, and the patient’s reasons for not adopting advanced diabetes technology (see accompanying example of a transition summary) .

I kept the summary brief, at two pages, and piloted it with referring providers who were interested in using the summary and with related supporting services. I also sought buy-in from my institution. This meant that I needed pediatric and adult divisional leadership support, which offered me information technology, resources, and expertise to automate the summary within the electronic health record. Once I had feedback from would-be users, we revised and updated the summary. We set up training for staff, including pediatric providers, nurse practitioners, social workers, and nurses who could fill out the summary, and ultimately succeeded in making it mandatory that the adult-care provider receive a summary before scheduling or seeing the transfer patient.

I started out with a paper version, and once we’d refined the questions, we incorporated it into the electronic medical record.

The information we use in our summary is grouped under the following headings:

• Reason for transition.
• Diabetes type.
• Degree of diabetes control.
• Type of insulin therapy and supplies.
• Current and former insulin regimen: reasons for discontinuation of any therapies or reluctance to start any therapies.
• Diabetes health maintenance.
• Social history and support, including living situation, main social support network, child protective services involvement.
• Other pertinent medical surgical history, including psychiatric disease.

Tips and takeaways

Top of the list of takeaways is that you should make the final document work for you, your colleagues, and ultimately, your patients – customize it as you see fit, but be sure to keep it short and easy to fill out. Make a note as you start using it in practice of what you think might be missing from the chart and whether updates are needed. If you can, it’s a great idea to fold the transfer summary into the electronic medical record, though it’s not imperative. Care coordination is key to successful transfer of patients, whether from pediatric to adult care or hospital to home. A small change to work flow can result in a huge change in patient and provider satisfaction, as well as a reduction in visit times.
 

Dr. Agarwal is director of the Supporting Emerging Adults With Diabetes (SEAD) program at Montefiore Medical Center and assistant professor of medicine at Albert Einstein College of Medicine, New York. She reports no disclosures or financial conflicts of interest. Write to her at cenews@mdedge.com.

Diabetes is a complex disease with a range of nuanced therapy options and a plethora of risk factors that could significantly affect patient quality of life and long-term outcomes. From the outset, after diagnosis, a selected regimen has to be meticulously tailored to a patient’s clinical needs and monitored over time, and many other nonclinical variables, such as patient preference, social history, access to care, and support systems, as well as the cost of the drugs and its impact on the patient, must also be considered.

The increase in the incidence of youth-onset diabetes means that more young adults are making the transition from pediatric to adult care, and careful care coordination is paramount at the handover point to ensure that a full and complete account of the history gets transferred to the adult-care provider.

So how do you distill the information from all those records (on paper and online) that you’ve accumulated during the time you’ve been treating a young adult who is now transitioning to adult care?
 

Transition summary

One resource that can facilitate this handover is the transition summary. It effectively consolidates and packages the aforementioned aspects of care and patient history so that the adult-care provider does not have to collect the patient’s history from the start. The transition summary should not be confused with the discharge or medical summary, which focuses only on the preceding clinical care.

It is important to stress at this stage that collaboration between the pediatric- and adult-care providers is crucial to the success of such a summary, from its creation, to its implementation, and through the subsequent and inevitable revisions and updates.
 

Benefits all around

After we introduced the transition summary at my institution, we found that the average initial patient visit with the new adult-care provider decreased by 12 minutes (with a range of 6-19 min). The adult-care providers welcomed receiving such detailed, important patient information packaged in a concise and readily accessible format. It helped them identify the preceding care team members, which facilitated continuity of care, and it also helped them forge a better therapeutic relationship with the patient earlier on in their engagement.

We also learned that patients were more comfortable with the transition, and the referring providers were relieved and reassured that their patients would continue to receive personalized care with the new adult-care provider.

At a personal level, I found I was less stressed as I could spend better-quality clinical time with patients. And I got to eliminate those unwieldy stacks of medical records since getting buy-in from divisional and IT leadership enabled us to automate the entire process of information transfer.

It is important to note that the patient has to consent to release of medical records to other institutions.
 

Setting up the summary

At our clinic, I started out by adapting the transition summary from guidelines provided by the Endocrine Society to make a template. Then, in collaboration with my pediatric colleagues, I removed and added information so that the revised document would contain information that is vitally important and not readily available in the chart and would be feasible to fill out. For example, we included details such as the patient’s psychosocial history, an estimation of the patient barriers to diabetes management, family relationship issues, and the patient’s reasons for not adopting advanced diabetes technology (see accompanying example of a transition summary) .

I kept the summary brief, at two pages, and piloted it with referring providers who were interested in using the summary and with related supporting services. I also sought buy-in from my institution. This meant that I needed pediatric and adult divisional leadership support, which offered me information technology, resources, and expertise to automate the summary within the electronic health record. Once I had feedback from would-be users, we revised and updated the summary. We set up training for staff, including pediatric providers, nurse practitioners, social workers, and nurses who could fill out the summary, and ultimately succeeded in making it mandatory that the adult-care provider receive a summary before scheduling or seeing the transfer patient.

I started out with a paper version, and once we’d refined the questions, we incorporated it into the electronic medical record.

The information we use in our summary is grouped under the following headings:

• Reason for transition.
• Diabetes type.
• Degree of diabetes control.
• Type of insulin therapy and supplies.
• Current and former insulin regimen: reasons for discontinuation of any therapies or reluctance to start any therapies.
• Diabetes health maintenance.
• Social history and support, including living situation, main social support network, child protective services involvement.
• Other pertinent medical surgical history, including psychiatric disease.

Tips and takeaways

Top of the list of takeaways is that you should make the final document work for you, your colleagues, and ultimately, your patients – customize it as you see fit, but be sure to keep it short and easy to fill out. Make a note as you start using it in practice of what you think might be missing from the chart and whether updates are needed. If you can, it’s a great idea to fold the transfer summary into the electronic medical record, though it’s not imperative. Care coordination is key to successful transfer of patients, whether from pediatric to adult care or hospital to home. A small change to work flow can result in a huge change in patient and provider satisfaction, as well as a reduction in visit times.
 

Dr. Agarwal is director of the Supporting Emerging Adults With Diabetes (SEAD) program at Montefiore Medical Center and assistant professor of medicine at Albert Einstein College of Medicine, New York. She reports no disclosures or financial conflicts of interest. Write to her at cenews@mdedge.com.

Transgender men who were assigned female sex at birth show a similar response to ovarian stimulation as cisgender women, even after using testosterone, shows the first formal study of its kind in this patient group.

The transgender patients each had an average of 20 eggs retrieved, and all who transferred embryos eventually achieved a successful pregnancy and delivery, “representing the largest cohort of transgender male patients to be described in the literature thus far,” wrote Nina Resetkova, MD, and colleagues in their article, published in Fertility and Sterility.

The research has been hailed as groundbreaking.

Dr. Resetkova, a reproductive endocrinologist at Boston IVF, Beth Israel Deaconess Medical Center, said in an interview that “these new data show it is reasonable for transmen [female-to-male transition], even those who have used testosterone for some time, to undergo assisted reproductive technology [ART].

“We’ve found that there isn’t a decrease in oocyte retrieval and may actually be a slight increase. We found this to be remarkable,” she said, emphasizing that these findings should be very reassuring for transgender male patients concerned about fertility.

“Transmales worry that they’ve thrown in the towel, and by committing to testosterone have started on a pathway with no return, but these data suggest they still have options,” Dr. Resetkova explained.

“Our study shows that these patients can have ovarian stimulation outcomes that are similar to those of cisgender counterparts, and this seems to be true even in cases of patients who have already initiated hormonal transition with the use of testosterone,” she said.

The researcher hopes the results will encourage more referrals for transgender men wishing to explore their fertility options. “Previously, many doctors were reluctant to refer to a fertility practice if their transmale patient had already started testosterone therapy or they had been on it for several years,” she said.

In a comment, Joshua Safer, MD, a spokesperson on transgender issues for the Endocrine Society, said that “fertility compromise may represent the single largest risk of medical treatment for some transgender persons. At meetings and in personal communications, several clinical groups have reported successful egg harvest from transgender men.

“However, this is the first careful study of a defined cohort published formally. As such, it serves as an important reference in advancing transgender medical care,” noted Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York.

Need for guidance

Previously, there has been an assumption that transgender individuals were not interested in maintaining their reproductive potential, but this has proven untrue. “Several recent studies have demonstrated that transgender people do desire parenthood, or at the least wish to preserve that possibility,” noted Dr. Resetkova and colleagues.

Both the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology have issued opinions that transgender patients should have the same access to fertility options as cisgender patients and that fertility preservation options should be discussed before gender transition, they noted.

The first and key intervention needed is the ability to preserve fertility through the cryopreservation of gametes before medical or surgical transition. In transgender men, this can be done via oocyte, embryo, or ovarian tissue cryopreservation.

Dr. Resetkova and the team at Boston IVF realized there was no published evidence, bar a couple of case reports, to guide clinicians caring for transgender men who wanted to preserve their fertility.

To help fill the research gap, they drew data from a retrospective cohort using electronic medical records from a single large in vitro fertilization (IVF) clinic. The search was conducted from January 2010 to July 2018, because the first transgender man was treated at the clinic in 2010.

To be included in the study, the patient had to identify as a transgender man and have completed an ovarian stimulation cycle for oocyte cryopreservation, embryo cryopreservation, or intended uterine transfer.

“This is the first study to describe transgender cycle parameters and outcomes in such detail and scope,” the authors noted in their article.

The study aimed to investigate ART outcomes in a female-to-male transgender cohort (n = 26) who wished to preserve fertility through egg freezing and/or undergo IVF with the intention of pregnancy.

Each transgender man was matched with five cisgender women for age, body mass index, and anti-Müllerian hormone level, and egg yield was compared. The 130 cisgender women were in straight relationships where there was difficulty conceiving, mostly because of male-factor, or tubal-factor, infertility; cisgender women with ovulatory dysfunction were excluded.

Egg harvest and T

The transgender patients were aged 14-39 years, with an average age at cycle start of 28 years. Some patients had not yet undergone any form of medical transition but planned to do so after ART.

The majority (61%) had received testosterone hormonal therapy, and a small number had undergone surgery, for example mastectomy and reconstruction, but none had undergone a hysterectomy or ovary removal (so-called “bottom” or gender-reassignment surgery).

Prior to ART, all patients taking testosterone came off the hormone on average 4 months prior to starting treatment. The mean time on testosterone before seeking ART treatment was 3.7 years and ranged from 3 months to 17 years.

“All patients had intact uterus and ovaries, and all patients had gone through puberty and had not received puberty blocking. This was required for ovarian stimulation and egg freezing,” Dr. Resetkova explained in an interview.

Researchers tracked patient records for outcomes, including oocyte yield, number of mature oocytes, total gonadotropin dose, and peak estradiol levels.

A mean of 19.9 +/– 8.7 oocytes were retrieved per cycle in the transgender cohort, compared with 15.9 +/– 9.6 in the cisgender female group; peak estradiol levels were similar between the two groups. However, the total dose of gonadotropins used was higher in the transgender group compared with the cisgender group (3,892 IU vs. 2,599 IU).

Of the 26 transgender men, 16 had egg preservation (oocyte banking) only. Seven couples had fresh or frozen embryo transfers, with all achieving live births.

Among the patients who planned for IVF with embryo transfer, two intended to carry the pregnancy themselves and the remaining five transferred embryos to their cisgender female partner.

The authors noted that many of the transgender patients who ultimately did not choose to proceed with treatment did so because of the need to stop testosterone therapy before initiating a cycle or the burden of cost.

“For many transgender patients, stopping androgen therapy can be both physically and psychologically distressing, especially because many experience the resumption of menses,” they observed.

“A logical follow-up question is whether ovarian stimulation can be done with any measure of success without the cessation of testosterone,” they noted.

“Although our findings are certainly reassuring for patients who have already initiated androgens, they were still all required to stop therapy to proceed with stimulation. This is a barrier to access that should be investigated, and if overcome may increase utilization of ART by transgender male patients,” they wrote.

Dr. Safer said that, to his knowledge, “a couple of fertility groups ... have been clear that the egg harvest could take place while the transgender men were using testosterone.”

Higher yield

The results with regard to the use of testosterone prior to ART were particularly enlightening, said Dr. Resetkova, who noted that testosterone therapy did not seem to affect ovarian stimulation.

“Before this study, we did not know if long-term testosterone use had a negative impact on egg reserve but, remarkably, testosterone does not appear to have an effect on the ovarian reserve as measured by egg count,” she noted, although she acknowledged that the “study is small.”

“In fact, in some ways, it looks like testosterone might even have a beneficial effect on egg count with a trend towards a higher number of eggs in the transmales who used it,” she added.

But this is “speculative,” she acknowledged, given the low numbers.

Reflecting on why long-term testosterone use may have shown a trend towards greater egg retrieval, Dr. Resetkova explained that the environment might be more similar to an individual with underlying elevated testosterone as seen in polycystic ovarian syndrome, and she noted these patients typically have a higher egg yield during IVF therapy.

Commenting on the higher doses of gonadotropins used in transgender patients, Dr. Resetkova suggested there could be various reasons for this, given that dosing was at the physician’s discretion, including the possibility that they knew the patient only had one chance and therefore higher doses of gonadotropins may have been administered.

Furthermore, each round of treatment is expensive. The researcher stressed, however, there was no conclusion in this respect based on their data.

Puberty blocking and fertility

When asked whether a transgender man who had undergone puberty blocking before transitioning (i.e., someone who had not gone through natural puberty) would be able to follow a similar course to pregnancy as the study participants, Dr. Resetkova acknowledged that is a more challenging area.

“We have little data so it’s hard to be conclusive, but it’s unlikely these patients would have mature hormonal responses and the ovaries might be in a naive state,” she hypothesized. “I don’t know that they would retain so many options as someone who had gone through natural puberty.”

“However, there are research protocols in place at some academic institutions for transgender patients planning to undergo puberty blocking,” she observed.

Finally, referring to individuals who transition from male to female using estrogen therapy, Dr. Resetkova said that the quality of sperm production might be impaired with long-term estrogen exposure. She added that other centers are looking at this.

“As transgender individuals increasingly seek access to reproductive services, we seek to shed light on the optimal way to provide effective care to these patients,” Dr. Dr. Resetkova and colleagues conclude.

Dr. Resetkova has reported no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Resetkova N et al. Fertil Steril. 2019;112:858-65.

Transgender men who were assigned female sex at birth show a similar response to ovarian stimulation as cisgender women, even after using testosterone, shows the first formal study of its kind in this patient group.

The transgender patients each had an average of 20 eggs retrieved, and all who transferred embryos eventually achieved a successful pregnancy and delivery, “representing the largest cohort of transgender male patients to be described in the literature thus far,” wrote Nina Resetkova, MD, and colleagues in their article, published in Fertility and Sterility.

The research has been hailed as groundbreaking.

Dr. Resetkova, a reproductive endocrinologist at Boston IVF, Beth Israel Deaconess Medical Center, said in an interview that “these new data show it is reasonable for transmen [female-to-male transition], even those who have used testosterone for some time, to undergo assisted reproductive technology [ART].

“We’ve found that there isn’t a decrease in oocyte retrieval and may actually be a slight increase. We found this to be remarkable,” she said, emphasizing that these findings should be very reassuring for transgender male patients concerned about fertility.

“Transmales worry that they’ve thrown in the towel, and by committing to testosterone have started on a pathway with no return, but these data suggest they still have options,” Dr. Resetkova explained.

“Our study shows that these patients can have ovarian stimulation outcomes that are similar to those of cisgender counterparts, and this seems to be true even in cases of patients who have already initiated hormonal transition with the use of testosterone,” she said.

The researcher hopes the results will encourage more referrals for transgender men wishing to explore their fertility options. “Previously, many doctors were reluctant to refer to a fertility practice if their transmale patient had already started testosterone therapy or they had been on it for several years,” she said.

In a comment, Joshua Safer, MD, a spokesperson on transgender issues for the Endocrine Society, said that “fertility compromise may represent the single largest risk of medical treatment for some transgender persons. At meetings and in personal communications, several clinical groups have reported successful egg harvest from transgender men.

“However, this is the first careful study of a defined cohort published formally. As such, it serves as an important reference in advancing transgender medical care,” noted Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York.

Need for guidance

Previously, there has been an assumption that transgender individuals were not interested in maintaining their reproductive potential, but this has proven untrue. “Several recent studies have demonstrated that transgender people do desire parenthood, or at the least wish to preserve that possibility,” noted Dr. Resetkova and colleagues.

Both the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology have issued opinions that transgender patients should have the same access to fertility options as cisgender patients and that fertility preservation options should be discussed before gender transition, they noted.

The first and key intervention needed is the ability to preserve fertility through the cryopreservation of gametes before medical or surgical transition. In transgender men, this can be done via oocyte, embryo, or ovarian tissue cryopreservation.

Dr. Resetkova and the team at Boston IVF realized there was no published evidence, bar a couple of case reports, to guide clinicians caring for transgender men who wanted to preserve their fertility.

To help fill the research gap, they drew data from a retrospective cohort using electronic medical records from a single large in vitro fertilization (IVF) clinic. The search was conducted from January 2010 to July 2018, because the first transgender man was treated at the clinic in 2010.

To be included in the study, the patient had to identify as a transgender man and have completed an ovarian stimulation cycle for oocyte cryopreservation, embryo cryopreservation, or intended uterine transfer.

“This is the first study to describe transgender cycle parameters and outcomes in such detail and scope,” the authors noted in their article.

The study aimed to investigate ART outcomes in a female-to-male transgender cohort (n = 26) who wished to preserve fertility through egg freezing and/or undergo IVF with the intention of pregnancy.

Each transgender man was matched with five cisgender women for age, body mass index, and anti-Müllerian hormone level, and egg yield was compared. The 130 cisgender women were in straight relationships where there was difficulty conceiving, mostly because of male-factor, or tubal-factor, infertility; cisgender women with ovulatory dysfunction were excluded.

Egg harvest and T

The transgender patients were aged 14-39 years, with an average age at cycle start of 28 years. Some patients had not yet undergone any form of medical transition but planned to do so after ART.

The majority (61%) had received testosterone hormonal therapy, and a small number had undergone surgery, for example mastectomy and reconstruction, but none had undergone a hysterectomy or ovary removal (so-called “bottom” or gender-reassignment surgery).

Prior to ART, all patients taking testosterone came off the hormone on average 4 months prior to starting treatment. The mean time on testosterone before seeking ART treatment was 3.7 years and ranged from 3 months to 17 years.

“All patients had intact uterus and ovaries, and all patients had gone through puberty and had not received puberty blocking. This was required for ovarian stimulation and egg freezing,” Dr. Resetkova explained in an interview.

Researchers tracked patient records for outcomes, including oocyte yield, number of mature oocytes, total gonadotropin dose, and peak estradiol levels.

A mean of 19.9 +/– 8.7 oocytes were retrieved per cycle in the transgender cohort, compared with 15.9 +/– 9.6 in the cisgender female group; peak estradiol levels were similar between the two groups. However, the total dose of gonadotropins used was higher in the transgender group compared with the cisgender group (3,892 IU vs. 2,599 IU).

Of the 26 transgender men, 16 had egg preservation (oocyte banking) only. Seven couples had fresh or frozen embryo transfers, with all achieving live births.

Among the patients who planned for IVF with embryo transfer, two intended to carry the pregnancy themselves and the remaining five transferred embryos to their cisgender female partner.

The authors noted that many of the transgender patients who ultimately did not choose to proceed with treatment did so because of the need to stop testosterone therapy before initiating a cycle or the burden of cost.

“For many transgender patients, stopping androgen therapy can be both physically and psychologically distressing, especially because many experience the resumption of menses,” they observed.

“A logical follow-up question is whether ovarian stimulation can be done with any measure of success without the cessation of testosterone,” they noted.

“Although our findings are certainly reassuring for patients who have already initiated androgens, they were still all required to stop therapy to proceed with stimulation. This is a barrier to access that should be investigated, and if overcome may increase utilization of ART by transgender male patients,” they wrote.

Dr. Safer said that, to his knowledge, “a couple of fertility groups ... have been clear that the egg harvest could take place while the transgender men were using testosterone.”

Higher yield

The results with regard to the use of testosterone prior to ART were particularly enlightening, said Dr. Resetkova, who noted that testosterone therapy did not seem to affect ovarian stimulation.

“Before this study, we did not know if long-term testosterone use had a negative impact on egg reserve but, remarkably, testosterone does not appear to have an effect on the ovarian reserve as measured by egg count,” she noted, although she acknowledged that the “study is small.”

“In fact, in some ways, it looks like testosterone might even have a beneficial effect on egg count with a trend towards a higher number of eggs in the transmales who used it,” she added.

But this is “speculative,” she acknowledged, given the low numbers.

Reflecting on why long-term testosterone use may have shown a trend towards greater egg retrieval, Dr. Resetkova explained that the environment might be more similar to an individual with underlying elevated testosterone as seen in polycystic ovarian syndrome, and she noted these patients typically have a higher egg yield during IVF therapy.

Commenting on the higher doses of gonadotropins used in transgender patients, Dr. Resetkova suggested there could be various reasons for this, given that dosing was at the physician’s discretion, including the possibility that they knew the patient only had one chance and therefore higher doses of gonadotropins may have been administered.

Furthermore, each round of treatment is expensive. The researcher stressed, however, there was no conclusion in this respect based on their data.

Puberty blocking and fertility

When asked whether a transgender man who had undergone puberty blocking before transitioning (i.e., someone who had not gone through natural puberty) would be able to follow a similar course to pregnancy as the study participants, Dr. Resetkova acknowledged that is a more challenging area.

“We have little data so it’s hard to be conclusive, but it’s unlikely these patients would have mature hormonal responses and the ovaries might be in a naive state,” she hypothesized. “I don’t know that they would retain so many options as someone who had gone through natural puberty.”

“However, there are research protocols in place at some academic institutions for transgender patients planning to undergo puberty blocking,” she observed.

Finally, referring to individuals who transition from male to female using estrogen therapy, Dr. Resetkova said that the quality of sperm production might be impaired with long-term estrogen exposure. She added that other centers are looking at this.

“As transgender individuals increasingly seek access to reproductive services, we seek to shed light on the optimal way to provide effective care to these patients,” Dr. Dr. Resetkova and colleagues conclude.

Dr. Resetkova has reported no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Resetkova N et al. Fertil Steril. 2019;112:858-65.

Transgender men who were assigned female sex at birth show a similar response to ovarian stimulation as cisgender women, even after using testosterone, shows the first formal study of its kind in this patient group.

The transgender patients each had an average of 20 eggs retrieved, and all who transferred embryos eventually achieved a successful pregnancy and delivery, “representing the largest cohort of transgender male patients to be described in the literature thus far,” wrote Nina Resetkova, MD, and colleagues in their article, published in Fertility and Sterility.

The research has been hailed as groundbreaking.

Dr. Resetkova, a reproductive endocrinologist at Boston IVF, Beth Israel Deaconess Medical Center, said in an interview that “these new data show it is reasonable for transmen [female-to-male transition], even those who have used testosterone for some time, to undergo assisted reproductive technology [ART].

“We’ve found that there isn’t a decrease in oocyte retrieval and may actually be a slight increase. We found this to be remarkable,” she said, emphasizing that these findings should be very reassuring for transgender male patients concerned about fertility.

“Transmales worry that they’ve thrown in the towel, and by committing to testosterone have started on a pathway with no return, but these data suggest they still have options,” Dr. Resetkova explained.

“Our study shows that these patients can have ovarian stimulation outcomes that are similar to those of cisgender counterparts, and this seems to be true even in cases of patients who have already initiated hormonal transition with the use of testosterone,” she said.

The researcher hopes the results will encourage more referrals for transgender men wishing to explore their fertility options. “Previously, many doctors were reluctant to refer to a fertility practice if their transmale patient had already started testosterone therapy or they had been on it for several years,” she said.

In a comment, Joshua Safer, MD, a spokesperson on transgender issues for the Endocrine Society, said that “fertility compromise may represent the single largest risk of medical treatment for some transgender persons. At meetings and in personal communications, several clinical groups have reported successful egg harvest from transgender men.

“However, this is the first careful study of a defined cohort published formally. As such, it serves as an important reference in advancing transgender medical care,” noted Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York.

Need for guidance

Previously, there has been an assumption that transgender individuals were not interested in maintaining their reproductive potential, but this has proven untrue. “Several recent studies have demonstrated that transgender people do desire parenthood, or at the least wish to preserve that possibility,” noted Dr. Resetkova and colleagues.

Both the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology have issued opinions that transgender patients should have the same access to fertility options as cisgender patients and that fertility preservation options should be discussed before gender transition, they noted.

The first and key intervention needed is the ability to preserve fertility through the cryopreservation of gametes before medical or surgical transition. In transgender men, this can be done via oocyte, embryo, or ovarian tissue cryopreservation.

Dr. Resetkova and the team at Boston IVF realized there was no published evidence, bar a couple of case reports, to guide clinicians caring for transgender men who wanted to preserve their fertility.

To help fill the research gap, they drew data from a retrospective cohort using electronic medical records from a single large in vitro fertilization (IVF) clinic. The search was conducted from January 2010 to July 2018, because the first transgender man was treated at the clinic in 2010.

To be included in the study, the patient had to identify as a transgender man and have completed an ovarian stimulation cycle for oocyte cryopreservation, embryo cryopreservation, or intended uterine transfer.

“This is the first study to describe transgender cycle parameters and outcomes in such detail and scope,” the authors noted in their article.

The study aimed to investigate ART outcomes in a female-to-male transgender cohort (n = 26) who wished to preserve fertility through egg freezing and/or undergo IVF with the intention of pregnancy.

Each transgender man was matched with five cisgender women for age, body mass index, and anti-Müllerian hormone level, and egg yield was compared. The 130 cisgender women were in straight relationships where there was difficulty conceiving, mostly because of male-factor, or tubal-factor, infertility; cisgender women with ovulatory dysfunction were excluded.

Egg harvest and T

The transgender patients were aged 14-39 years, with an average age at cycle start of 28 years. Some patients had not yet undergone any form of medical transition but planned to do so after ART.

The majority (61%) had received testosterone hormonal therapy, and a small number had undergone surgery, for example mastectomy and reconstruction, but none had undergone a hysterectomy or ovary removal (so-called “bottom” or gender-reassignment surgery).

Prior to ART, all patients taking testosterone came off the hormone on average 4 months prior to starting treatment. The mean time on testosterone before seeking ART treatment was 3.7 years and ranged from 3 months to 17 years.

“All patients had intact uterus and ovaries, and all patients had gone through puberty and had not received puberty blocking. This was required for ovarian stimulation and egg freezing,” Dr. Resetkova explained in an interview.

Researchers tracked patient records for outcomes, including oocyte yield, number of mature oocytes, total gonadotropin dose, and peak estradiol levels.

A mean of 19.9 +/– 8.7 oocytes were retrieved per cycle in the transgender cohort, compared with 15.9 +/– 9.6 in the cisgender female group; peak estradiol levels were similar between the two groups. However, the total dose of gonadotropins used was higher in the transgender group compared with the cisgender group (3,892 IU vs. 2,599 IU).

Of the 26 transgender men, 16 had egg preservation (oocyte banking) only. Seven couples had fresh or frozen embryo transfers, with all achieving live births.

Among the patients who planned for IVF with embryo transfer, two intended to carry the pregnancy themselves and the remaining five transferred embryos to their cisgender female partner.

The authors noted that many of the transgender patients who ultimately did not choose to proceed with treatment did so because of the need to stop testosterone therapy before initiating a cycle or the burden of cost.

“For many transgender patients, stopping androgen therapy can be both physically and psychologically distressing, especially because many experience the resumption of menses,” they observed.

“A logical follow-up question is whether ovarian stimulation can be done with any measure of success without the cessation of testosterone,” they noted.

“Although our findings are certainly reassuring for patients who have already initiated androgens, they were still all required to stop therapy to proceed with stimulation. This is a barrier to access that should be investigated, and if overcome may increase utilization of ART by transgender male patients,” they wrote.

Dr. Safer said that, to his knowledge, “a couple of fertility groups ... have been clear that the egg harvest could take place while the transgender men were using testosterone.”

Higher yield

The results with regard to the use of testosterone prior to ART were particularly enlightening, said Dr. Resetkova, who noted that testosterone therapy did not seem to affect ovarian stimulation.

“Before this study, we did not know if long-term testosterone use had a negative impact on egg reserve but, remarkably, testosterone does not appear to have an effect on the ovarian reserve as measured by egg count,” she noted, although she acknowledged that the “study is small.”

“In fact, in some ways, it looks like testosterone might even have a beneficial effect on egg count with a trend towards a higher number of eggs in the transmales who used it,” she added.

But this is “speculative,” she acknowledged, given the low numbers.

Reflecting on why long-term testosterone use may have shown a trend towards greater egg retrieval, Dr. Resetkova explained that the environment might be more similar to an individual with underlying elevated testosterone as seen in polycystic ovarian syndrome, and she noted these patients typically have a higher egg yield during IVF therapy.

Commenting on the higher doses of gonadotropins used in transgender patients, Dr. Resetkova suggested there could be various reasons for this, given that dosing was at the physician’s discretion, including the possibility that they knew the patient only had one chance and therefore higher doses of gonadotropins may have been administered.

Furthermore, each round of treatment is expensive. The researcher stressed, however, there was no conclusion in this respect based on their data.

Puberty blocking and fertility

When asked whether a transgender man who had undergone puberty blocking before transitioning (i.e., someone who had not gone through natural puberty) would be able to follow a similar course to pregnancy as the study participants, Dr. Resetkova acknowledged that is a more challenging area.

“We have little data so it’s hard to be conclusive, but it’s unlikely these patients would have mature hormonal responses and the ovaries might be in a naive state,” she hypothesized. “I don’t know that they would retain so many options as someone who had gone through natural puberty.”

“However, there are research protocols in place at some academic institutions for transgender patients planning to undergo puberty blocking,” she observed.

Finally, referring to individuals who transition from male to female using estrogen therapy, Dr. Resetkova said that the quality of sperm production might be impaired with long-term estrogen exposure. She added that other centers are looking at this.

“As transgender individuals increasingly seek access to reproductive services, we seek to shed light on the optimal way to provide effective care to these patients,” Dr. Dr. Resetkova and colleagues conclude.

Dr. Resetkova has reported no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Resetkova N et al. Fertil Steril. 2019;112:858-65.

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

LOS ANGELES – Although menopausal hormone therapy is not approved for the prevention of type 2 diabetes because of its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms, according to Franck Mauvais-Jarvis, MD.

Doug Brunk/MDedge News

“During the menopause transition, women accumulate metabolic disturbances, including visceral obesity, systemic inflammation, insulin resistance, dyslipidemia, and hypertension,” Dr. Mauvais-Jarvis, director of the Tulane Diabetes Research Program at Tulane University Health Sciences Center, New Orleans, said at the Annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They also lose muscle mass. Some of these abnormalities are partially explained by chronological aging, but they are also caused by estrogen deficiency. There’s a synergism between aging and estrogen deficiency.”

The best evidence of this synergy comes from older trials. Nearly 30 years ago, researchers examined the association between postmenopausal hormone use and the subsequent incidence of non–insulin dependent diabetes in a prospective cohort of 21,028 postmenopausal U.S. women aged 30-55 years, who were enrolled in the Nurse’s Health Study and followed for 12 years (Ann Epidemiol. 1992;2[5]:665-73). They found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes. In a more recent trial, researchers examined the association between use of hormone therapy and new-onset diabetes in 63,624 postmenopausal women who were enrolled in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) and followed for 15 years (Diabetologia. 2009;52[10]:2092-100). It found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes.

In the Heart and Estrogen/Progestin Replacement Study, researchers evaluated the effect of hormone therapy on fasting glucose level and incident diabetes in 2,763 postmenopausal women with coronary heart disease (Ann Intern Med. 2003;138[1]:1-9). At 20 U.S. centers, the study participants received 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone, or placebo, and were followed for 4 years. The researchers found that the use of hormone therapy reduced the incidence of diabetes by 35%.

According to Dr. Mauvais-Jarvis, the strongest data come from the Women’s Health Initiative (WHI), a randomized, double-blind trial that compared the effect of daily 0.625 mg conjugated estrogen plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up (Diabetologia. 2004; 47[7]:1175-87). It showed a 20% decrease in the incidence of diabetes at 5 years. More recently, researchers found that, whether WHI participants took estrogen plus medroxyprogesterone or estrogen alone, the protection from diabetes was present (N Engl J Med. 2016;374:803-6).

In 2006, researchers published results from a meta-analysis of 107 trials in an effort to quantify the effects of hormone therapy on components of metabolic syndrome in postmenopausal women (Diabetes Obes Metab. 2006;8[5]:538-54). In women without diabetes, hormone therapy reduced the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score by 13% and incidence of type 2 diabetes by 30%. In women with diabetes, hormone therapy reduced fasting glucose by 11% and HOMA-IR by 36%.

The mechanisms by which estrogens improve glucose homeostasis are yet to be fully understood. “One of the most important [mechanisms] is a decrease in abdominal fat, which improves insulin resistance and systemic inflammation,” Dr. Mauvais-Jarvis said. “However, in the WHI, it was clear that the improvement in HOMA-IR was independent from the body weight and fat. Estrogen has also been found to increase insulin clearance and sensitivity, increase glucose disposal and effectiveness and decrease sarcopenia. There are fewer than 20 studies looking at beta-cell function. Half of them have shown that estrogen improves insulin secretion.”

Route of estrogen administration also comes into play. For example, oral estrogens increase liver exposure to estrogen, increase triglycerides, and increase clotting factors. “That is why oral estrogens are not indicated in women with risk of deep venous thrombosis,” Dr. Mauvais-Jarvis said. “They also increase inflammatory factors like C-reactive protein. Advantages are that they decrease LDL cholesterol levels and increase HDL cholesterol levels more than transdermal estrogen does.”

The main advantage with transdermal delivery of estrogen, he continued, is that it does not raise triglycerides, clotting factors, or inflammatory factors, and it confers less exposure to the liver. “That’s why it’s the preferred way of administration in women who are obese, who have a risk of DVT, or who have cardiovascular risk factors,” he said. “It has a lower suppression of hepatic glucose production, it increases circulating estradiol, and the delivery to nonhepatic tissue is increased. The oral form of estrogen is cheaper, compared with the transdermal form, though. This is a factor that is always taken into account.”

Dr. Mauvais-Jarvis and colleagues were first to evaluate the effect of conjugated estrogens plus bazedoxifene in mice (Mol Metab. 2014;3[2]:177-90). “The idea was that by combining estrogen and bazedoxifene, you have the beneficial effect of estrogen in the tissues but you block estrogen in the breast and in the uterus, and therefore, you prevent the risk of cancer,” he said. “We found that tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. It increased energy expenditure and decreased fatty liver.”

In a subsequent pilot study, he and his colleagues assessed the effect of 12 weeks’ treatment with bazedoxifene/conjugated estrogens, compared with placebo, on glucose homeostasis and body composition in 12 postmenopausal women (NCT02237079). “We did not find any significant alterations in the IVGTT [Intravenous Glucose Tolerance Test] but we observed improved fasting beta-cell function and serum glucose in menopausal women with obesity,” Dr. Mauvais-Jarvis said (J Endocr Soc. 2019;3[8]:1583-94).

In a separate, randomized, double-blind, placebo-controlled, crossover trial that he and his colleagues performed in eight postmenopausal women with obesity, the primary endpoint was insulin action as measured by a two-step hyperinsulinemic-euglycemic clamp. Secondary endpoints were body composition, basal metabolic rate, ectopic fat, and metabolome. “We did not find any difference in systemic insulin action, ectopic fat, or energy expenditure,” he said. “But we found something very interesting. We did a metabolic analysis and found that oral estrogens increase hepatic de novo lipogenesis and liver triacylglycerol production. In other words, the oral estrogens were increasing [triacylglycerol] synthesis from glucose, but it does not accumulate in the liver.”

Dr. Mauvais-Jarvis disclosed that he has received research support from the National Institutes of Health, the American Diabetes Association, the Department of Veterans Affairs, and Pfizer.
 

dbrunk@mdedge.com

LOS ANGELES – Although menopausal hormone therapy is not approved for the prevention of type 2 diabetes because of its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms, according to Franck Mauvais-Jarvis, MD.

Doug Brunk/MDedge News

“During the menopause transition, women accumulate metabolic disturbances, including visceral obesity, systemic inflammation, insulin resistance, dyslipidemia, and hypertension,” Dr. Mauvais-Jarvis, director of the Tulane Diabetes Research Program at Tulane University Health Sciences Center, New Orleans, said at the Annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They also lose muscle mass. Some of these abnormalities are partially explained by chronological aging, but they are also caused by estrogen deficiency. There’s a synergism between aging and estrogen deficiency.”

The best evidence of this synergy comes from older trials. Nearly 30 years ago, researchers examined the association between postmenopausal hormone use and the subsequent incidence of non–insulin dependent diabetes in a prospective cohort of 21,028 postmenopausal U.S. women aged 30-55 years, who were enrolled in the Nurse’s Health Study and followed for 12 years (Ann Epidemiol. 1992;2[5]:665-73). They found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes. In a more recent trial, researchers examined the association between use of hormone therapy and new-onset diabetes in 63,624 postmenopausal women who were enrolled in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) and followed for 15 years (Diabetologia. 2009;52[10]:2092-100). It found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes.

In the Heart and Estrogen/Progestin Replacement Study, researchers evaluated the effect of hormone therapy on fasting glucose level and incident diabetes in 2,763 postmenopausal women with coronary heart disease (Ann Intern Med. 2003;138[1]:1-9). At 20 U.S. centers, the study participants received 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone, or placebo, and were followed for 4 years. The researchers found that the use of hormone therapy reduced the incidence of diabetes by 35%.

According to Dr. Mauvais-Jarvis, the strongest data come from the Women’s Health Initiative (WHI), a randomized, double-blind trial that compared the effect of daily 0.625 mg conjugated estrogen plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up (Diabetologia. 2004; 47[7]:1175-87). It showed a 20% decrease in the incidence of diabetes at 5 years. More recently, researchers found that, whether WHI participants took estrogen plus medroxyprogesterone or estrogen alone, the protection from diabetes was present (N Engl J Med. 2016;374:803-6).

In 2006, researchers published results from a meta-analysis of 107 trials in an effort to quantify the effects of hormone therapy on components of metabolic syndrome in postmenopausal women (Diabetes Obes Metab. 2006;8[5]:538-54). In women without diabetes, hormone therapy reduced the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score by 13% and incidence of type 2 diabetes by 30%. In women with diabetes, hormone therapy reduced fasting glucose by 11% and HOMA-IR by 36%.

The mechanisms by which estrogens improve glucose homeostasis are yet to be fully understood. “One of the most important [mechanisms] is a decrease in abdominal fat, which improves insulin resistance and systemic inflammation,” Dr. Mauvais-Jarvis said. “However, in the WHI, it was clear that the improvement in HOMA-IR was independent from the body weight and fat. Estrogen has also been found to increase insulin clearance and sensitivity, increase glucose disposal and effectiveness and decrease sarcopenia. There are fewer than 20 studies looking at beta-cell function. Half of them have shown that estrogen improves insulin secretion.”

Route of estrogen administration also comes into play. For example, oral estrogens increase liver exposure to estrogen, increase triglycerides, and increase clotting factors. “That is why oral estrogens are not indicated in women with risk of deep venous thrombosis,” Dr. Mauvais-Jarvis said. “They also increase inflammatory factors like C-reactive protein. Advantages are that they decrease LDL cholesterol levels and increase HDL cholesterol levels more than transdermal estrogen does.”

The main advantage with transdermal delivery of estrogen, he continued, is that it does not raise triglycerides, clotting factors, or inflammatory factors, and it confers less exposure to the liver. “That’s why it’s the preferred way of administration in women who are obese, who have a risk of DVT, or who have cardiovascular risk factors,” he said. “It has a lower suppression of hepatic glucose production, it increases circulating estradiol, and the delivery to nonhepatic tissue is increased. The oral form of estrogen is cheaper, compared with the transdermal form, though. This is a factor that is always taken into account.”

Dr. Mauvais-Jarvis and colleagues were first to evaluate the effect of conjugated estrogens plus bazedoxifene in mice (Mol Metab. 2014;3[2]:177-90). “The idea was that by combining estrogen and bazedoxifene, you have the beneficial effect of estrogen in the tissues but you block estrogen in the breast and in the uterus, and therefore, you prevent the risk of cancer,” he said. “We found that tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. It increased energy expenditure and decreased fatty liver.”

In a subsequent pilot study, he and his colleagues assessed the effect of 12 weeks’ treatment with bazedoxifene/conjugated estrogens, compared with placebo, on glucose homeostasis and body composition in 12 postmenopausal women (NCT02237079). “We did not find any significant alterations in the IVGTT [Intravenous Glucose Tolerance Test] but we observed improved fasting beta-cell function and serum glucose in menopausal women with obesity,” Dr. Mauvais-Jarvis said (J Endocr Soc. 2019;3[8]:1583-94).

In a separate, randomized, double-blind, placebo-controlled, crossover trial that he and his colleagues performed in eight postmenopausal women with obesity, the primary endpoint was insulin action as measured by a two-step hyperinsulinemic-euglycemic clamp. Secondary endpoints were body composition, basal metabolic rate, ectopic fat, and metabolome. “We did not find any difference in systemic insulin action, ectopic fat, or energy expenditure,” he said. “But we found something very interesting. We did a metabolic analysis and found that oral estrogens increase hepatic de novo lipogenesis and liver triacylglycerol production. In other words, the oral estrogens were increasing [triacylglycerol] synthesis from glucose, but it does not accumulate in the liver.”

Dr. Mauvais-Jarvis disclosed that he has received research support from the National Institutes of Health, the American Diabetes Association, the Department of Veterans Affairs, and Pfizer.
 

dbrunk@mdedge.com

LOS ANGELES – Although menopausal hormone therapy is not approved for the prevention of type 2 diabetes because of its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms, according to Franck Mauvais-Jarvis, MD.

Doug Brunk/MDedge News

“During the menopause transition, women accumulate metabolic disturbances, including visceral obesity, systemic inflammation, insulin resistance, dyslipidemia, and hypertension,” Dr. Mauvais-Jarvis, director of the Tulane Diabetes Research Program at Tulane University Health Sciences Center, New Orleans, said at the Annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They also lose muscle mass. Some of these abnormalities are partially explained by chronological aging, but they are also caused by estrogen deficiency. There’s a synergism between aging and estrogen deficiency.”

The best evidence of this synergy comes from older trials. Nearly 30 years ago, researchers examined the association between postmenopausal hormone use and the subsequent incidence of non–insulin dependent diabetes in a prospective cohort of 21,028 postmenopausal U.S. women aged 30-55 years, who were enrolled in the Nurse’s Health Study and followed for 12 years (Ann Epidemiol. 1992;2[5]:665-73). They found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes. In a more recent trial, researchers examined the association between use of hormone therapy and new-onset diabetes in 63,624 postmenopausal women who were enrolled in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) and followed for 15 years (Diabetologia. 2009;52[10]:2092-100). It found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes.

In the Heart and Estrogen/Progestin Replacement Study, researchers evaluated the effect of hormone therapy on fasting glucose level and incident diabetes in 2,763 postmenopausal women with coronary heart disease (Ann Intern Med. 2003;138[1]:1-9). At 20 U.S. centers, the study participants received 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone, or placebo, and were followed for 4 years. The researchers found that the use of hormone therapy reduced the incidence of diabetes by 35%.

According to Dr. Mauvais-Jarvis, the strongest data come from the Women’s Health Initiative (WHI), a randomized, double-blind trial that compared the effect of daily 0.625 mg conjugated estrogen plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up (Diabetologia. 2004; 47[7]:1175-87). It showed a 20% decrease in the incidence of diabetes at 5 years. More recently, researchers found that, whether WHI participants took estrogen plus medroxyprogesterone or estrogen alone, the protection from diabetes was present (N Engl J Med. 2016;374:803-6).

In 2006, researchers published results from a meta-analysis of 107 trials in an effort to quantify the effects of hormone therapy on components of metabolic syndrome in postmenopausal women (Diabetes Obes Metab. 2006;8[5]:538-54). In women without diabetes, hormone therapy reduced the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score by 13% and incidence of type 2 diabetes by 30%. In women with diabetes, hormone therapy reduced fasting glucose by 11% and HOMA-IR by 36%.

The mechanisms by which estrogens improve glucose homeostasis are yet to be fully understood. “One of the most important [mechanisms] is a decrease in abdominal fat, which improves insulin resistance and systemic inflammation,” Dr. Mauvais-Jarvis said. “However, in the WHI, it was clear that the improvement in HOMA-IR was independent from the body weight and fat. Estrogen has also been found to increase insulin clearance and sensitivity, increase glucose disposal and effectiveness and decrease sarcopenia. There are fewer than 20 studies looking at beta-cell function. Half of them have shown that estrogen improves insulin secretion.”

Route of estrogen administration also comes into play. For example, oral estrogens increase liver exposure to estrogen, increase triglycerides, and increase clotting factors. “That is why oral estrogens are not indicated in women with risk of deep venous thrombosis,” Dr. Mauvais-Jarvis said. “They also increase inflammatory factors like C-reactive protein. Advantages are that they decrease LDL cholesterol levels and increase HDL cholesterol levels more than transdermal estrogen does.”

The main advantage with transdermal delivery of estrogen, he continued, is that it does not raise triglycerides, clotting factors, or inflammatory factors, and it confers less exposure to the liver. “That’s why it’s the preferred way of administration in women who are obese, who have a risk of DVT, or who have cardiovascular risk factors,” he said. “It has a lower suppression of hepatic glucose production, it increases circulating estradiol, and the delivery to nonhepatic tissue is increased. The oral form of estrogen is cheaper, compared with the transdermal form, though. This is a factor that is always taken into account.”

Dr. Mauvais-Jarvis and colleagues were first to evaluate the effect of conjugated estrogens plus bazedoxifene in mice (Mol Metab. 2014;3[2]:177-90). “The idea was that by combining estrogen and bazedoxifene, you have the beneficial effect of estrogen in the tissues but you block estrogen in the breast and in the uterus, and therefore, you prevent the risk of cancer,” he said. “We found that tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. It increased energy expenditure and decreased fatty liver.”

In a subsequent pilot study, he and his colleagues assessed the effect of 12 weeks’ treatment with bazedoxifene/conjugated estrogens, compared with placebo, on glucose homeostasis and body composition in 12 postmenopausal women (NCT02237079). “We did not find any significant alterations in the IVGTT [Intravenous Glucose Tolerance Test] but we observed improved fasting beta-cell function and serum glucose in menopausal women with obesity,” Dr. Mauvais-Jarvis said (J Endocr Soc. 2019;3[8]:1583-94).

In a separate, randomized, double-blind, placebo-controlled, crossover trial that he and his colleagues performed in eight postmenopausal women with obesity, the primary endpoint was insulin action as measured by a two-step hyperinsulinemic-euglycemic clamp. Secondary endpoints were body composition, basal metabolic rate, ectopic fat, and metabolome. “We did not find any difference in systemic insulin action, ectopic fat, or energy expenditure,” he said. “But we found something very interesting. We did a metabolic analysis and found that oral estrogens increase hepatic de novo lipogenesis and liver triacylglycerol production. In other words, the oral estrogens were increasing [triacylglycerol] synthesis from glucose, but it does not accumulate in the liver.”

Dr. Mauvais-Jarvis disclosed that he has received research support from the National Institutes of Health, the American Diabetes Association, the Department of Veterans Affairs, and Pfizer.
 

dbrunk@mdedge.com

WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.

If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.

“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.

Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”

ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.

Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”

In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”

ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
 

Glyburide’s role

Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”

As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.

One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).

A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”

The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).

That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.

Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.

The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
 

Metformin outcomes

Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).

A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.

Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”

Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.

In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”

The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.

But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
 

Offspring well-being

Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)

Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.

A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).

A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).

That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).

In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).

WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.

If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.

“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.

Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”

ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.

Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”

In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”

ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
 

Glyburide’s role

Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”

As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.

One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).

A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”

The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).

That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.

Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.

The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
 

Metformin outcomes

Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).

A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.

Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”

Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.

In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”

The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.

But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
 

Offspring well-being

Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)

Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.

A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).

A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).

That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).

In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).

WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.

If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.

“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.

Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”

ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.

Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”

In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”

ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
 

Glyburide’s role

Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”

As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.

One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).

A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”

The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).

That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.

Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.

The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
 

Metformin outcomes

Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).

A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.

Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”

Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.

In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”

The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.

But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
 

Offspring well-being

Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)

Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.

A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).

A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).

That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).

In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.