MDedge Endocrinology

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Pediatrician Michelle Collins-Ogle, MD, already has a busy practice helping young people address questions about their gender identity. She has treated more than 230 patients over the past 2 years at Children’s Hospital at Montefiore in the Bronx, New York.

Dr. Collins-Ogle specializes in adolescent medicine in New York, a state without the restrictions on such care that have been enacted in roughly half the country.

On December 13, 2023, Ohio lawmakers passed a bill banning gender-affirming medical care to minors which Gov. Mike DeWine vetoed on December 29. Another 26 states have similar restrictions in place, according to a tally provided to this news organization by the Human Rights Campaign, which tracks this issue.

Clinicians like Dr. Collins-Ogle are feeling the impact. In her practice, Dr. Collins-Ogle met a couple that moved from Texas to New York to allow their child to access gender-affirming medical care.

“They wanted their child to be able to receive medical care, but they also were afraid for their own safety, of having their child taken from them, and being locked up,” Dr. Collins-Ogle told this news organization. 

With patients have also come protestors and harassment. In fact, many physicians are reluctant to speak on this topic amid a recent spate of threats. Psychiatric News reported that conservative pundits and high-profile social media accounts have targeted physicians who provide gender-affirming medical care, spurring harassment campaigns against clinics in cities such as Akron, Boston, and Nashville. “The attackers asserted that the clinics were mutilating children and giving them ‘chemical castration drugs,’ among other claims,” the Psychiatric News reported.

This news organization contacted more than a half dozen organizations that provide gender-affirming care for adolescents and teens seeking interviews about the effects of these restrictions.

All but Montefiore’s Dr. Collins-Ogle turned down the request.

“If my kids are brave enough to come see me, I can’t cower,” Dr. Collins-Ogle said. 

But Dr. Collins-Ogle emphasized she understands why many fellow physicians are concerned about speaking publicly about gender-affirming medical care. 
 

Dissenters Spread Misinformation and Threats

Recent years have seen increasing politicization of this issue, often due to inaccurate depictions of gender-affirming medical care circulating on social media. 

In 2022, the American Medical Association (AMA), the American Academy of Pediatrics (AAP), and the Children’s Hospital Association asked the Justice Department to investigate what they called “increasing threats of violence against physicians, hospitals, and families of children for providing and seeking evidence-based gender-affirming care.” 

The three organizations also called on X (formerly known as Twitter), TikTok, and Meta, which owns Facebook and Instagram, to do more to address coordinated campaigns of disinformation. 

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence,” said Moira Szilagyi, MD, PhD, then AAP president in a statement. 
 

Medical Groups Defend Care to Prevent Suicide

The AAP, AMA, and other influential medical associations are banding together to fight new legal restrictions on gender-affirming medical care for teens and adolescents. (These briefs do not discuss surgeries typically available for adults.) 

Since 2022, these medical organizations have filed amicus briefs in cases challenging new restrictions put in place in Arkansas, Alabama, Florida, Georgia, Idaho, Indiana, Kentucky, North Dakota, Oklahoma, Tennessee, and Texas. 

Other signers to the amicus briefs: 

• Academic Pediatric Association
• American Academy of Child & Adolescent Psychiatry
• American Academy of Family Physicians
• American Academy of Nursing
• GLMA: Health Professionals Advancing LGBTQ+ Equality
• American College of Obstetricians and Gynecologists
• American College of Osteopathic Pediatricians
• The American College of Physicians
• American Pediatric Society
• Association of Medical School Pediatric Department Chairs, Inc.
• Endocrine Society
• National Association of Pediatric Nurse Practitioners
• The Pediatric Endocrine Society, Societies for Pediatric Urology
• Society for Adolescent Health and Medicine
• Society for Pediatric Research
• The Society of Pediatric Nurses
• World Professional Association for Transgender Health

In these amicus briefs, the medical groups argue that evidence-based guidelines support the use of medication in treating gender dysphoria. The amicus briefs in particular cite an Endocrine Society guideline and the standards of care developed by the World Professional Association for Transgender Health (WPATH).

Research shows that adolescents with gender dysphoria who receive puberty blockers and other medications experience less depression, anxiety, and suicidal ideation, the groups have said.

“In light of this evidence supporting the connection between lack of access to gender-affirming care and lifetime suicide risk, banning such care can put patients’ lives at risk,” the AAP and other groups said.
 

Debate Over Source of Gender Identity Concerns 

Having doubts and concerns about one’s gender remains a relatively rare phenomena, although it appears more common among younger people. 

Among US adults, 0.5% or about 1.3 million people identify as transgender whereas about 1.4% or about 300,000 people in the 13-17–year-old group do so, according to a report issued in 2022 by the Williams Institute of the UCLA School of Law. 
 

Questionable Diagnosis Drives Bans on Care

The term “rapid-onset gender dysphoria,” referring to young people who suddenly question their gender as part of peer group dynamics, persists in political debates. The conservative Heritage Foundation has used the term as well as “social contagion” in its effort to seek restrictions on gender-affirming care for young people. 

Ohio Rep. Gary Click, a Republican, said at an April 2023 hearing that his Save Adolescents from Experimentation (SAFE) bill would prevent teens from being harmed due to “social contagion” or “ rapid-onset gender dysphoria.” 

The bill, which the Ohio legislature cleared in December, would block physicians from starting new patients on puberty blockers. (It also bars surgeries as part of gender-affirming medical care, although hospital officials and physicians told lawmakers these are not done in Ohio.) 

Among the groups opposing Click’s bill were the Ohio chapter of the AAP, the Ohio State Medical Association and several hospitals and hospital groups as well as physicians speaking independently. 

Gender-Affirming Care ‘Buys Time’ to Avoid Impulsive Decisions

Kate Krueck, MD, a pediatrician with a practice in the Columbus area, testified about her experience as the mother of a transgender child who once attempted suicide. 

“It wasn’t always easy to reconstruct my vision of a baby with a vagina into the adolescent before me with a new name and changed pronouns, but they were still the same incredible person,” Krueck said. 

She urged lawmakers to understand how puberty blockers can “buy time” for teens to cope with a body at odds with their vision of themselves, noting that many of the effects of these medications are largely reversible. The side effects that are not reversible, such as facial hair growth and the growth of Adam’s Apple, are certainly outweighed by the risks of withholding treatment, she said. 
 

Bad Patient Experience Drives Detractor Activist

Arguing against that point was Chloe Cole, a detransitioner activist who had returned to a female identity. At the Ohio legislative hearings, Ms. Cole spoke of her experience in California as a teen treated for gender dysphoria.

“I was fast-tracked by medical butchers starting at 13 when I was given cross sex hormones, and they took my breasts away from me at 15 years old,” she said.

Ms. Cole appears frequently to testify in favor of bans on gender-affirming medical care. In 2022, she told the Ohio lawmakers about her experience of attending a class with about a dozen other young people in the midst of female-to-male transitions. She now sees that class as having inadvertently helped reinforce her decision to have her breasts removed.

“Despite all these consultations and classes, I don’t feel like I understood all the ramifications that came with any of the medical decisions I was making,” Ms. Cole said. “I didn’t realize how traumatic the recovery would be, and it wasn’t until I was almost a year post-op that I realized I may want to breastfeed my future children; I will never be able to do that.”

Ms. Cole also spoke in July before the US House subcommittee on the Constitution and Limited Government.

“I look in the mirror sometimes, and I feel like a monster,” Ms. Cole said at the House hearing, which was titled “ The Dangers and Due Process Violations of ‘Gender-Affirming Care’.” 

During the hearing, Shannon Minter, legal director of the National Center for Lesbian Rights (NCLR), who also made a gender transition, thanked Ms. Cole but noted that her case is an exception.

A 2022 Lancet Child and Adolescent Health article reported that 704 (98%) people in the Netherlands who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Ms. Minter credits this high rate of continuation to clinicians taking their duties to adolescents seriously. 

State legislatures and medical boards oversee the regulation of medical practice in the US. But a few Republicans in both chambers of the US Congress have shown an interest in enacting a federal ban restricting physicians’ ability to provide gender-affirming medical care. 

They include Rep. Mike Johnson of Louisiana, who in October 2023 became Speaker of the House. He chaired the July hearing at which Ms. Cole spoke. He’s also a sponsor of a House bill introduced by Rep. Marjorie Taylor Greene (R-GA). 

This measure, which has the support of 45 House Republicans, would make it a felony to perform any gender-affirming care on a minor, and it permits a minor on whom such care is performed to bring a civil action against each individual who provided the care. Sen. JD Vance (R-OH) introduced the companion Senate measure.
 

Reality of Gender-Affirming Care

The drive to pass laws like those in Ohio and Arkansas stem from a lack of knowledge about gender-affirming treatments, including a false idea that doctors prescribe medications at teens’ requests, Montefiore’s Dr. Collins-Ogle said. 

“There’s a misperception that young people will say ‘I’m transgender’ and that those of us who provide care are just giving them hormones or whatever they want. It’s not true, and it doesn’t happen that way,” Dr. Collins-Ogle said. 

At the Children’s Hospital at Montefiore, Dr. Collins-Ogle said her work with patients wrestling with gender identity issues begins with questions. 

“What’s your understanding of dysphoria? Where’s the incongruence between the gender you were assigned at birth and what you’re feeling now? You have to be able to verbalize that” before the treatment proceeds, she said. 

Sometimes teens leave after an initial conversation and then return later when they have a more clearly defined sense of what dysphoria means. 

“There are other kids who clearly, clearly understand that the gender they were assigned at birth is not who they are,” she said. 

Children now wrestle with added concerns that their parents could be put at risk for trying to help them, she said. 

“These kids go through so much. And we have these people in powerful positions telling them that they don’t matter and telling them, ‘We’re going to cut off your access to healthcare, Medicaid; if your parents tried to seek out this care for you, we’re going to put them in jail,’” she said. 

“It’s the biggest factor in fear mongering,” she said. 

Dr. Collins-Ogle said she wonders why legislators who lack medical training are trying to dictate how physicians can practice. 

“I took a Hippocratic oath to do no harm. I have a medical board that I answer to,” she said. “I don’t understand how legislators can get away with legislating about something they know nothing about.”

A version of this article appeared on Medscape.com.

Pediatrician Michelle Collins-Ogle, MD, already has a busy practice helping young people address questions about their gender identity. She has treated more than 230 patients over the past 2 years at Children’s Hospital at Montefiore in the Bronx, New York.

Dr. Collins-Ogle specializes in adolescent medicine in New York, a state without the restrictions on such care that have been enacted in roughly half the country.

On December 13, 2023, Ohio lawmakers passed a bill banning gender-affirming medical care to minors which Gov. Mike DeWine vetoed on December 29. Another 26 states have similar restrictions in place, according to a tally provided to this news organization by the Human Rights Campaign, which tracks this issue.

Clinicians like Dr. Collins-Ogle are feeling the impact. In her practice, Dr. Collins-Ogle met a couple that moved from Texas to New York to allow their child to access gender-affirming medical care.

“They wanted their child to be able to receive medical care, but they also were afraid for their own safety, of having their child taken from them, and being locked up,” Dr. Collins-Ogle told this news organization. 

With patients have also come protestors and harassment. In fact, many physicians are reluctant to speak on this topic amid a recent spate of threats. Psychiatric News reported that conservative pundits and high-profile social media accounts have targeted physicians who provide gender-affirming medical care, spurring harassment campaigns against clinics in cities such as Akron, Boston, and Nashville. “The attackers asserted that the clinics were mutilating children and giving them ‘chemical castration drugs,’ among other claims,” the Psychiatric News reported.

This news organization contacted more than a half dozen organizations that provide gender-affirming care for adolescents and teens seeking interviews about the effects of these restrictions.

All but Montefiore’s Dr. Collins-Ogle turned down the request.

“If my kids are brave enough to come see me, I can’t cower,” Dr. Collins-Ogle said. 

But Dr. Collins-Ogle emphasized she understands why many fellow physicians are concerned about speaking publicly about gender-affirming medical care. 
 

Dissenters Spread Misinformation and Threats

Recent years have seen increasing politicization of this issue, often due to inaccurate depictions of gender-affirming medical care circulating on social media. 

In 2022, the American Medical Association (AMA), the American Academy of Pediatrics (AAP), and the Children’s Hospital Association asked the Justice Department to investigate what they called “increasing threats of violence against physicians, hospitals, and families of children for providing and seeking evidence-based gender-affirming care.” 

The three organizations also called on X (formerly known as Twitter), TikTok, and Meta, which owns Facebook and Instagram, to do more to address coordinated campaigns of disinformation. 

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence,” said Moira Szilagyi, MD, PhD, then AAP president in a statement. 
 

Medical Groups Defend Care to Prevent Suicide

The AAP, AMA, and other influential medical associations are banding together to fight new legal restrictions on gender-affirming medical care for teens and adolescents. (These briefs do not discuss surgeries typically available for adults.) 

Since 2022, these medical organizations have filed amicus briefs in cases challenging new restrictions put in place in Arkansas, Alabama, Florida, Georgia, Idaho, Indiana, Kentucky, North Dakota, Oklahoma, Tennessee, and Texas. 

Other signers to the amicus briefs: 

• Academic Pediatric Association
• American Academy of Child & Adolescent Psychiatry
• American Academy of Family Physicians
• American Academy of Nursing
• GLMA: Health Professionals Advancing LGBTQ+ Equality
• American College of Obstetricians and Gynecologists
• American College of Osteopathic Pediatricians
• The American College of Physicians
• American Pediatric Society
• Association of Medical School Pediatric Department Chairs, Inc.
• Endocrine Society
• National Association of Pediatric Nurse Practitioners
• The Pediatric Endocrine Society, Societies for Pediatric Urology
• Society for Adolescent Health and Medicine
• Society for Pediatric Research
• The Society of Pediatric Nurses
• World Professional Association for Transgender Health

In these amicus briefs, the medical groups argue that evidence-based guidelines support the use of medication in treating gender dysphoria. The amicus briefs in particular cite an Endocrine Society guideline and the standards of care developed by the World Professional Association for Transgender Health (WPATH).

Research shows that adolescents with gender dysphoria who receive puberty blockers and other medications experience less depression, anxiety, and suicidal ideation, the groups have said.

“In light of this evidence supporting the connection between lack of access to gender-affirming care and lifetime suicide risk, banning such care can put patients’ lives at risk,” the AAP and other groups said.
 

Debate Over Source of Gender Identity Concerns 

Having doubts and concerns about one’s gender remains a relatively rare phenomena, although it appears more common among younger people. 

Among US adults, 0.5% or about 1.3 million people identify as transgender whereas about 1.4% or about 300,000 people in the 13-17–year-old group do so, according to a report issued in 2022 by the Williams Institute of the UCLA School of Law. 
 

Questionable Diagnosis Drives Bans on Care

The term “rapid-onset gender dysphoria,” referring to young people who suddenly question their gender as part of peer group dynamics, persists in political debates. The conservative Heritage Foundation has used the term as well as “social contagion” in its effort to seek restrictions on gender-affirming care for young people. 

Ohio Rep. Gary Click, a Republican, said at an April 2023 hearing that his Save Adolescents from Experimentation (SAFE) bill would prevent teens from being harmed due to “social contagion” or “ rapid-onset gender dysphoria.” 

The bill, which the Ohio legislature cleared in December, would block physicians from starting new patients on puberty blockers. (It also bars surgeries as part of gender-affirming medical care, although hospital officials and physicians told lawmakers these are not done in Ohio.) 

Among the groups opposing Click’s bill were the Ohio chapter of the AAP, the Ohio State Medical Association and several hospitals and hospital groups as well as physicians speaking independently. 

Gender-Affirming Care ‘Buys Time’ to Avoid Impulsive Decisions

Kate Krueck, MD, a pediatrician with a practice in the Columbus area, testified about her experience as the mother of a transgender child who once attempted suicide. 

“It wasn’t always easy to reconstruct my vision of a baby with a vagina into the adolescent before me with a new name and changed pronouns, but they were still the same incredible person,” Krueck said. 

She urged lawmakers to understand how puberty blockers can “buy time” for teens to cope with a body at odds with their vision of themselves, noting that many of the effects of these medications are largely reversible. The side effects that are not reversible, such as facial hair growth and the growth of Adam’s Apple, are certainly outweighed by the risks of withholding treatment, she said. 
 

Bad Patient Experience Drives Detractor Activist

Arguing against that point was Chloe Cole, a detransitioner activist who had returned to a female identity. At the Ohio legislative hearings, Ms. Cole spoke of her experience in California as a teen treated for gender dysphoria.

“I was fast-tracked by medical butchers starting at 13 when I was given cross sex hormones, and they took my breasts away from me at 15 years old,” she said.

Ms. Cole appears frequently to testify in favor of bans on gender-affirming medical care. In 2022, she told the Ohio lawmakers about her experience of attending a class with about a dozen other young people in the midst of female-to-male transitions. She now sees that class as having inadvertently helped reinforce her decision to have her breasts removed.

“Despite all these consultations and classes, I don’t feel like I understood all the ramifications that came with any of the medical decisions I was making,” Ms. Cole said. “I didn’t realize how traumatic the recovery would be, and it wasn’t until I was almost a year post-op that I realized I may want to breastfeed my future children; I will never be able to do that.”

Ms. Cole also spoke in July before the US House subcommittee on the Constitution and Limited Government.

“I look in the mirror sometimes, and I feel like a monster,” Ms. Cole said at the House hearing, which was titled “ The Dangers and Due Process Violations of ‘Gender-Affirming Care’.” 

During the hearing, Shannon Minter, legal director of the National Center for Lesbian Rights (NCLR), who also made a gender transition, thanked Ms. Cole but noted that her case is an exception.

A 2022 Lancet Child and Adolescent Health article reported that 704 (98%) people in the Netherlands who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Ms. Minter credits this high rate of continuation to clinicians taking their duties to adolescents seriously. 

State legislatures and medical boards oversee the regulation of medical practice in the US. But a few Republicans in both chambers of the US Congress have shown an interest in enacting a federal ban restricting physicians’ ability to provide gender-affirming medical care. 

They include Rep. Mike Johnson of Louisiana, who in October 2023 became Speaker of the House. He chaired the July hearing at which Ms. Cole spoke. He’s also a sponsor of a House bill introduced by Rep. Marjorie Taylor Greene (R-GA). 

This measure, which has the support of 45 House Republicans, would make it a felony to perform any gender-affirming care on a minor, and it permits a minor on whom such care is performed to bring a civil action against each individual who provided the care. Sen. JD Vance (R-OH) introduced the companion Senate measure.
 

Reality of Gender-Affirming Care

The drive to pass laws like those in Ohio and Arkansas stem from a lack of knowledge about gender-affirming treatments, including a false idea that doctors prescribe medications at teens’ requests, Montefiore’s Dr. Collins-Ogle said. 

“There’s a misperception that young people will say ‘I’m transgender’ and that those of us who provide care are just giving them hormones or whatever they want. It’s not true, and it doesn’t happen that way,” Dr. Collins-Ogle said. 

At the Children’s Hospital at Montefiore, Dr. Collins-Ogle said her work with patients wrestling with gender identity issues begins with questions. 

“What’s your understanding of dysphoria? Where’s the incongruence between the gender you were assigned at birth and what you’re feeling now? You have to be able to verbalize that” before the treatment proceeds, she said. 

Sometimes teens leave after an initial conversation and then return later when they have a more clearly defined sense of what dysphoria means. 

“There are other kids who clearly, clearly understand that the gender they were assigned at birth is not who they are,” she said. 

Children now wrestle with added concerns that their parents could be put at risk for trying to help them, she said. 

“These kids go through so much. And we have these people in powerful positions telling them that they don’t matter and telling them, ‘We’re going to cut off your access to healthcare, Medicaid; if your parents tried to seek out this care for you, we’re going to put them in jail,’” she said. 

“It’s the biggest factor in fear mongering,” she said. 

Dr. Collins-Ogle said she wonders why legislators who lack medical training are trying to dictate how physicians can practice. 

“I took a Hippocratic oath to do no harm. I have a medical board that I answer to,” she said. “I don’t understand how legislators can get away with legislating about something they know nothing about.”

A version of this article appeared on Medscape.com.

Pediatrician Michelle Collins-Ogle, MD, already has a busy practice helping young people address questions about their gender identity. She has treated more than 230 patients over the past 2 years at Children’s Hospital at Montefiore in the Bronx, New York.

Dr. Collins-Ogle specializes in adolescent medicine in New York, a state without the restrictions on such care that have been enacted in roughly half the country.

On December 13, 2023, Ohio lawmakers passed a bill banning gender-affirming medical care to minors which Gov. Mike DeWine vetoed on December 29. Another 26 states have similar restrictions in place, according to a tally provided to this news organization by the Human Rights Campaign, which tracks this issue.

Clinicians like Dr. Collins-Ogle are feeling the impact. In her practice, Dr. Collins-Ogle met a couple that moved from Texas to New York to allow their child to access gender-affirming medical care.

“They wanted their child to be able to receive medical care, but they also were afraid for their own safety, of having their child taken from them, and being locked up,” Dr. Collins-Ogle told this news organization. 

With patients have also come protestors and harassment. In fact, many physicians are reluctant to speak on this topic amid a recent spate of threats. Psychiatric News reported that conservative pundits and high-profile social media accounts have targeted physicians who provide gender-affirming medical care, spurring harassment campaigns against clinics in cities such as Akron, Boston, and Nashville. “The attackers asserted that the clinics were mutilating children and giving them ‘chemical castration drugs,’ among other claims,” the Psychiatric News reported.

This news organization contacted more than a half dozen organizations that provide gender-affirming care for adolescents and teens seeking interviews about the effects of these restrictions.

All but Montefiore’s Dr. Collins-Ogle turned down the request.

“If my kids are brave enough to come see me, I can’t cower,” Dr. Collins-Ogle said. 

But Dr. Collins-Ogle emphasized she understands why many fellow physicians are concerned about speaking publicly about gender-affirming medical care. 
 

Dissenters Spread Misinformation and Threats

Recent years have seen increasing politicization of this issue, often due to inaccurate depictions of gender-affirming medical care circulating on social media. 

In 2022, the American Medical Association (AMA), the American Academy of Pediatrics (AAP), and the Children’s Hospital Association asked the Justice Department to investigate what they called “increasing threats of violence against physicians, hospitals, and families of children for providing and seeking evidence-based gender-affirming care.” 

The three organizations also called on X (formerly known as Twitter), TikTok, and Meta, which owns Facebook and Instagram, to do more to address coordinated campaigns of disinformation. 

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence,” said Moira Szilagyi, MD, PhD, then AAP president in a statement. 
 

Medical Groups Defend Care to Prevent Suicide

The AAP, AMA, and other influential medical associations are banding together to fight new legal restrictions on gender-affirming medical care for teens and adolescents. (These briefs do not discuss surgeries typically available for adults.) 

Since 2022, these medical organizations have filed amicus briefs in cases challenging new restrictions put in place in Arkansas, Alabama, Florida, Georgia, Idaho, Indiana, Kentucky, North Dakota, Oklahoma, Tennessee, and Texas. 

Other signers to the amicus briefs: 

• Academic Pediatric Association
• American Academy of Child & Adolescent Psychiatry
• American Academy of Family Physicians
• American Academy of Nursing
• GLMA: Health Professionals Advancing LGBTQ+ Equality
• American College of Obstetricians and Gynecologists
• American College of Osteopathic Pediatricians
• The American College of Physicians
• American Pediatric Society
• Association of Medical School Pediatric Department Chairs, Inc.
• Endocrine Society
• National Association of Pediatric Nurse Practitioners
• The Pediatric Endocrine Society, Societies for Pediatric Urology
• Society for Adolescent Health and Medicine
• Society for Pediatric Research
• The Society of Pediatric Nurses
• World Professional Association for Transgender Health

In these amicus briefs, the medical groups argue that evidence-based guidelines support the use of medication in treating gender dysphoria. The amicus briefs in particular cite an Endocrine Society guideline and the standards of care developed by the World Professional Association for Transgender Health (WPATH).

Research shows that adolescents with gender dysphoria who receive puberty blockers and other medications experience less depression, anxiety, and suicidal ideation, the groups have said.

“In light of this evidence supporting the connection between lack of access to gender-affirming care and lifetime suicide risk, banning such care can put patients’ lives at risk,” the AAP and other groups said.
 

Debate Over Source of Gender Identity Concerns 

Having doubts and concerns about one’s gender remains a relatively rare phenomena, although it appears more common among younger people. 

Among US adults, 0.5% or about 1.3 million people identify as transgender whereas about 1.4% or about 300,000 people in the 13-17–year-old group do so, according to a report issued in 2022 by the Williams Institute of the UCLA School of Law. 
 

Questionable Diagnosis Drives Bans on Care

The term “rapid-onset gender dysphoria,” referring to young people who suddenly question their gender as part of peer group dynamics, persists in political debates. The conservative Heritage Foundation has used the term as well as “social contagion” in its effort to seek restrictions on gender-affirming care for young people. 

Ohio Rep. Gary Click, a Republican, said at an April 2023 hearing that his Save Adolescents from Experimentation (SAFE) bill would prevent teens from being harmed due to “social contagion” or “ rapid-onset gender dysphoria.” 

The bill, which the Ohio legislature cleared in December, would block physicians from starting new patients on puberty blockers. (It also bars surgeries as part of gender-affirming medical care, although hospital officials and physicians told lawmakers these are not done in Ohio.) 

Among the groups opposing Click’s bill were the Ohio chapter of the AAP, the Ohio State Medical Association and several hospitals and hospital groups as well as physicians speaking independently. 

Gender-Affirming Care ‘Buys Time’ to Avoid Impulsive Decisions

Kate Krueck, MD, a pediatrician with a practice in the Columbus area, testified about her experience as the mother of a transgender child who once attempted suicide. 

“It wasn’t always easy to reconstruct my vision of a baby with a vagina into the adolescent before me with a new name and changed pronouns, but they were still the same incredible person,” Krueck said. 

She urged lawmakers to understand how puberty blockers can “buy time” for teens to cope with a body at odds with their vision of themselves, noting that many of the effects of these medications are largely reversible. The side effects that are not reversible, such as facial hair growth and the growth of Adam’s Apple, are certainly outweighed by the risks of withholding treatment, she said. 
 

Bad Patient Experience Drives Detractor Activist

Arguing against that point was Chloe Cole, a detransitioner activist who had returned to a female identity. At the Ohio legislative hearings, Ms. Cole spoke of her experience in California as a teen treated for gender dysphoria.

“I was fast-tracked by medical butchers starting at 13 when I was given cross sex hormones, and they took my breasts away from me at 15 years old,” she said.

Ms. Cole appears frequently to testify in favor of bans on gender-affirming medical care. In 2022, she told the Ohio lawmakers about her experience of attending a class with about a dozen other young people in the midst of female-to-male transitions. She now sees that class as having inadvertently helped reinforce her decision to have her breasts removed.

“Despite all these consultations and classes, I don’t feel like I understood all the ramifications that came with any of the medical decisions I was making,” Ms. Cole said. “I didn’t realize how traumatic the recovery would be, and it wasn’t until I was almost a year post-op that I realized I may want to breastfeed my future children; I will never be able to do that.”

Ms. Cole also spoke in July before the US House subcommittee on the Constitution and Limited Government.

“I look in the mirror sometimes, and I feel like a monster,” Ms. Cole said at the House hearing, which was titled “ The Dangers and Due Process Violations of ‘Gender-Affirming Care’.” 

During the hearing, Shannon Minter, legal director of the National Center for Lesbian Rights (NCLR), who also made a gender transition, thanked Ms. Cole but noted that her case is an exception.

A 2022 Lancet Child and Adolescent Health article reported that 704 (98%) people in the Netherlands who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Ms. Minter credits this high rate of continuation to clinicians taking their duties to adolescents seriously. 

State legislatures and medical boards oversee the regulation of medical practice in the US. But a few Republicans in both chambers of the US Congress have shown an interest in enacting a federal ban restricting physicians’ ability to provide gender-affirming medical care. 

They include Rep. Mike Johnson of Louisiana, who in October 2023 became Speaker of the House. He chaired the July hearing at which Ms. Cole spoke. He’s also a sponsor of a House bill introduced by Rep. Marjorie Taylor Greene (R-GA). 

This measure, which has the support of 45 House Republicans, would make it a felony to perform any gender-affirming care on a minor, and it permits a minor on whom such care is performed to bring a civil action against each individual who provided the care. Sen. JD Vance (R-OH) introduced the companion Senate measure.
 

Reality of Gender-Affirming Care

The drive to pass laws like those in Ohio and Arkansas stem from a lack of knowledge about gender-affirming treatments, including a false idea that doctors prescribe medications at teens’ requests, Montefiore’s Dr. Collins-Ogle said. 

“There’s a misperception that young people will say ‘I’m transgender’ and that those of us who provide care are just giving them hormones or whatever they want. It’s not true, and it doesn’t happen that way,” Dr. Collins-Ogle said. 

At the Children’s Hospital at Montefiore, Dr. Collins-Ogle said her work with patients wrestling with gender identity issues begins with questions. 

“What’s your understanding of dysphoria? Where’s the incongruence between the gender you were assigned at birth and what you’re feeling now? You have to be able to verbalize that” before the treatment proceeds, she said. 

Sometimes teens leave after an initial conversation and then return later when they have a more clearly defined sense of what dysphoria means. 

“There are other kids who clearly, clearly understand that the gender they were assigned at birth is not who they are,” she said. 

Children now wrestle with added concerns that their parents could be put at risk for trying to help them, she said. 

“These kids go through so much. And we have these people in powerful positions telling them that they don’t matter and telling them, ‘We’re going to cut off your access to healthcare, Medicaid; if your parents tried to seek out this care for you, we’re going to put them in jail,’” she said. 

“It’s the biggest factor in fear mongering,” she said. 

Dr. Collins-Ogle said she wonders why legislators who lack medical training are trying to dictate how physicians can practice. 

“I took a Hippocratic oath to do no harm. I have a medical board that I answer to,” she said. “I don’t understand how legislators can get away with legislating about something they know nothing about.”

A version of this article appeared on Medscape.com.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.