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Acne before puberty: When to treat, when to worry
NEWPORT BEACH, CALIF. – according to Sheila Fallon Friedlander, MD.
“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
Neonatal acne (ages birth to 4 weeks)
Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.
The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”
Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.
As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.
Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
Infantile acne (ages 0-12 months)
This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.
In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”
However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.
As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.
Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
Midchildhood (ages 1-7 years)
“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”
Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.
It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”
Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.
Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
Prepubertal acne (ages 7 years to puberty)
Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.
Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.
Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”
Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – according to Sheila Fallon Friedlander, MD.
“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
Neonatal acne (ages birth to 4 weeks)
Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.
The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”
Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.
As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.
Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
Infantile acne (ages 0-12 months)
This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.
In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”
However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.
As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.
Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
Midchildhood (ages 1-7 years)
“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”
Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.
It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”
Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.
Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
Prepubertal acne (ages 7 years to puberty)
Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.
Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.
Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”
Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – according to Sheila Fallon Friedlander, MD.
“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
Neonatal acne (ages birth to 4 weeks)
Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.
The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”
Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.
As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.
Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
Infantile acne (ages 0-12 months)
This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.
In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”
However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.
As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.
Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
Midchildhood (ages 1-7 years)
“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”
Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.
It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”
Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.
Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
Prepubertal acne (ages 7 years to puberty)
Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.
Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.
Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”
Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.
REPORTING FROM SDEF WOMEN’S & PEDIATRIC DERMATOLOGY SEMINAR
Caution is key when pregnancy and psoriasis mix
NEWPORT BEACH, CALIF. – Psoriasis often clears in pregnant women, giving them a rare break from the skin disease. But
Data from 2011 found 45% of pregnancies in U.S. women aged 15-44 years were unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52), cautioned Jashin J. Wu, MD, of Dermatology Research and Education Foundation, Irvine, Calif.
In a presentation at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar, Dr. Wu offered these tips about pregnancy and psoriasis:
Counsel patients before pregnancy
There’s conflicting data about the risks of psoriasis in pregnancy, Dr. Wu said. One 23-year-old study suggests a link to adverse outcomes such as preterm and low-birth-weight babies. But another more recent study found no sign of increased risk (Int J Dermatol. 1996;35:169-72; J Am Acad Dermatol. 2011;64:71-7).
Counseling can include information about risks such as hospitalization during pregnancy because of undertreatment of psoriasis, he said. Discuss lowering medication doses to the lowest effective dose, he recommended, and talk about alternatives to systemic medications.
Make adjustments to timing as needed
In patients with severe cases, it may be appropriate to recommend that they postpone pregnancy until their psoriasis is under better control. As for treatment of psoriasis, “you may want to consider timing medication to end around the first trimester to get the medication out of them during the greatest risk period for the baby,” Dr. Wu said.
Adjust steroids as necessary
There are no “good” studies about the use of steroids in pregnant women with psoriasis, Dr. Wu said. “We can probably assume they are safe overall. Weaker steroids may have less risk,” and some of the stronger steroids may raise concerns.
Dr. Wu made these recommendations: Limit mild-potency topical corticosteroids to less than 100 g/week, potent topical corticosteroids to less than 50 g/week, and superpotent topical corticosteroids to less than 30 g/week.
Some topical drugs appear to be OK
Vitamin D analogues have not been well-studied in pregnancy, he said, but “we consider topical use to be fairly safe.”
There’s no data on calcineurin inhibitors in pregnancy, he said, but topical use is considered to be safe because there’s limited systemic absorption.
Beware of certain drugs in pregnancyTazarotene is considered to be dangerous in pregnancy, Dr. Wu said, and females of childbearing age who take it should use effective contraception, and have a recent negative pregnancy test (within 2 weeks before treatment begins). “In general, I’d probably not use this,” he said. “We have so many other options.”
Data about pregnancy safety for three topical drugs – coal tar, anthralin, and salicylic acid – is limited or nonexistent, Dr. Wu said, and he recommends against their use in pregnancy.
Phototherapy is OK in pregnancy
Phototherapy is considered safe because UVB doesn’t penetrate the superficial layer of the skin, he said. But phototherapy brings a potential risk of lowered folic acid levels, and he urges folic acid supplementation in women undergoing the treatment who are considering pregnancy or who are in the first trimester.
Avoid certain systemic drugs
Dr. Wu offered these recommendations:
- Methotrexate: Do not take during pregnancy, or 3 months prior to conception.
- Acitretin (Soriatane): Avoid all use in women who may become pregnant.
- Cyclosporine: Be aware of reports of prematurity and low birth weight linked to the drug.
- Apremilast (Otezla): Animal studies have shown a risk in pregnancy. Stop the drug at least 2 days before conception.
Avoid monoclonal antibodies
These drugs “result in therapeutic levels in the fetus, which is not a good thing,” Dr. Wu said. “You obviously don’t want to have monoclonal antibodies in the baby.”
Nix the PUVA
While one study found no link between psoralen plus UVA (PUVA) and birth defects (Arch Dermatol. 1993 Mar;129[3]:320-3), there’s still a theoretical risk, Dr. Wu said. He recommended that the treatment be avoided during pregnancy.
Watch for waxing and waning
Dr. Wu pointed to a small 2005 study that suggested that psoriasis activity declines during pregnancy. The study used different measures, finding that psoriasis improved by 30% (based on at least a 3% change in body surface area) or 55% (based on patient self-reporting). But it flares after pregnancy as reported by 65% of women surveyed; a body surface area analysis found that psoriasis worsened in 41% (Arch Dermatol. 2005 May;141[5]:601-6).
Dr. Wu reports various relationships (research, consultation and speaking) with 15 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – Psoriasis often clears in pregnant women, giving them a rare break from the skin disease. But
Data from 2011 found 45% of pregnancies in U.S. women aged 15-44 years were unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52), cautioned Jashin J. Wu, MD, of Dermatology Research and Education Foundation, Irvine, Calif.
In a presentation at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar, Dr. Wu offered these tips about pregnancy and psoriasis:
Counsel patients before pregnancy
There’s conflicting data about the risks of psoriasis in pregnancy, Dr. Wu said. One 23-year-old study suggests a link to adverse outcomes such as preterm and low-birth-weight babies. But another more recent study found no sign of increased risk (Int J Dermatol. 1996;35:169-72; J Am Acad Dermatol. 2011;64:71-7).
Counseling can include information about risks such as hospitalization during pregnancy because of undertreatment of psoriasis, he said. Discuss lowering medication doses to the lowest effective dose, he recommended, and talk about alternatives to systemic medications.
Make adjustments to timing as needed
In patients with severe cases, it may be appropriate to recommend that they postpone pregnancy until their psoriasis is under better control. As for treatment of psoriasis, “you may want to consider timing medication to end around the first trimester to get the medication out of them during the greatest risk period for the baby,” Dr. Wu said.
Adjust steroids as necessary
There are no “good” studies about the use of steroids in pregnant women with psoriasis, Dr. Wu said. “We can probably assume they are safe overall. Weaker steroids may have less risk,” and some of the stronger steroids may raise concerns.
Dr. Wu made these recommendations: Limit mild-potency topical corticosteroids to less than 100 g/week, potent topical corticosteroids to less than 50 g/week, and superpotent topical corticosteroids to less than 30 g/week.
Some topical drugs appear to be OK
Vitamin D analogues have not been well-studied in pregnancy, he said, but “we consider topical use to be fairly safe.”
There’s no data on calcineurin inhibitors in pregnancy, he said, but topical use is considered to be safe because there’s limited systemic absorption.
Beware of certain drugs in pregnancyTazarotene is considered to be dangerous in pregnancy, Dr. Wu said, and females of childbearing age who take it should use effective contraception, and have a recent negative pregnancy test (within 2 weeks before treatment begins). “In general, I’d probably not use this,” he said. “We have so many other options.”
Data about pregnancy safety for three topical drugs – coal tar, anthralin, and salicylic acid – is limited or nonexistent, Dr. Wu said, and he recommends against their use in pregnancy.
Phototherapy is OK in pregnancy
Phototherapy is considered safe because UVB doesn’t penetrate the superficial layer of the skin, he said. But phototherapy brings a potential risk of lowered folic acid levels, and he urges folic acid supplementation in women undergoing the treatment who are considering pregnancy or who are in the first trimester.
Avoid certain systemic drugs
Dr. Wu offered these recommendations:
- Methotrexate: Do not take during pregnancy, or 3 months prior to conception.
- Acitretin (Soriatane): Avoid all use in women who may become pregnant.
- Cyclosporine: Be aware of reports of prematurity and low birth weight linked to the drug.
- Apremilast (Otezla): Animal studies have shown a risk in pregnancy. Stop the drug at least 2 days before conception.
Avoid monoclonal antibodies
These drugs “result in therapeutic levels in the fetus, which is not a good thing,” Dr. Wu said. “You obviously don’t want to have monoclonal antibodies in the baby.”
Nix the PUVA
While one study found no link between psoralen plus UVA (PUVA) and birth defects (Arch Dermatol. 1993 Mar;129[3]:320-3), there’s still a theoretical risk, Dr. Wu said. He recommended that the treatment be avoided during pregnancy.
Watch for waxing and waning
Dr. Wu pointed to a small 2005 study that suggested that psoriasis activity declines during pregnancy. The study used different measures, finding that psoriasis improved by 30% (based on at least a 3% change in body surface area) or 55% (based on patient self-reporting). But it flares after pregnancy as reported by 65% of women surveyed; a body surface area analysis found that psoriasis worsened in 41% (Arch Dermatol. 2005 May;141[5]:601-6).
Dr. Wu reports various relationships (research, consultation and speaking) with 15 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – Psoriasis often clears in pregnant women, giving them a rare break from the skin disease. But
Data from 2011 found 45% of pregnancies in U.S. women aged 15-44 years were unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52), cautioned Jashin J. Wu, MD, of Dermatology Research and Education Foundation, Irvine, Calif.
In a presentation at the Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar, Dr. Wu offered these tips about pregnancy and psoriasis:
Counsel patients before pregnancy
There’s conflicting data about the risks of psoriasis in pregnancy, Dr. Wu said. One 23-year-old study suggests a link to adverse outcomes such as preterm and low-birth-weight babies. But another more recent study found no sign of increased risk (Int J Dermatol. 1996;35:169-72; J Am Acad Dermatol. 2011;64:71-7).
Counseling can include information about risks such as hospitalization during pregnancy because of undertreatment of psoriasis, he said. Discuss lowering medication doses to the lowest effective dose, he recommended, and talk about alternatives to systemic medications.
Make adjustments to timing as needed
In patients with severe cases, it may be appropriate to recommend that they postpone pregnancy until their psoriasis is under better control. As for treatment of psoriasis, “you may want to consider timing medication to end around the first trimester to get the medication out of them during the greatest risk period for the baby,” Dr. Wu said.
Adjust steroids as necessary
There are no “good” studies about the use of steroids in pregnant women with psoriasis, Dr. Wu said. “We can probably assume they are safe overall. Weaker steroids may have less risk,” and some of the stronger steroids may raise concerns.
Dr. Wu made these recommendations: Limit mild-potency topical corticosteroids to less than 100 g/week, potent topical corticosteroids to less than 50 g/week, and superpotent topical corticosteroids to less than 30 g/week.
Some topical drugs appear to be OK
Vitamin D analogues have not been well-studied in pregnancy, he said, but “we consider topical use to be fairly safe.”
There’s no data on calcineurin inhibitors in pregnancy, he said, but topical use is considered to be safe because there’s limited systemic absorption.
Beware of certain drugs in pregnancyTazarotene is considered to be dangerous in pregnancy, Dr. Wu said, and females of childbearing age who take it should use effective contraception, and have a recent negative pregnancy test (within 2 weeks before treatment begins). “In general, I’d probably not use this,” he said. “We have so many other options.”
Data about pregnancy safety for three topical drugs – coal tar, anthralin, and salicylic acid – is limited or nonexistent, Dr. Wu said, and he recommends against their use in pregnancy.
Phototherapy is OK in pregnancy
Phototherapy is considered safe because UVB doesn’t penetrate the superficial layer of the skin, he said. But phototherapy brings a potential risk of lowered folic acid levels, and he urges folic acid supplementation in women undergoing the treatment who are considering pregnancy or who are in the first trimester.
Avoid certain systemic drugs
Dr. Wu offered these recommendations:
- Methotrexate: Do not take during pregnancy, or 3 months prior to conception.
- Acitretin (Soriatane): Avoid all use in women who may become pregnant.
- Cyclosporine: Be aware of reports of prematurity and low birth weight linked to the drug.
- Apremilast (Otezla): Animal studies have shown a risk in pregnancy. Stop the drug at least 2 days before conception.
Avoid monoclonal antibodies
These drugs “result in therapeutic levels in the fetus, which is not a good thing,” Dr. Wu said. “You obviously don’t want to have monoclonal antibodies in the baby.”
Nix the PUVA
While one study found no link between psoralen plus UVA (PUVA) and birth defects (Arch Dermatol. 1993 Mar;129[3]:320-3), there’s still a theoretical risk, Dr. Wu said. He recommended that the treatment be avoided during pregnancy.
Watch for waxing and waning
Dr. Wu pointed to a small 2005 study that suggested that psoriasis activity declines during pregnancy. The study used different measures, finding that psoriasis improved by 30% (based on at least a 3% change in body surface area) or 55% (based on patient self-reporting). But it flares after pregnancy as reported by 65% of women surveyed; a body surface area analysis found that psoriasis worsened in 41% (Arch Dermatol. 2005 May;141[5]:601-6).
Dr. Wu reports various relationships (research, consultation and speaking) with 15 pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF WOMEN’S & PEDIATRIC DERMATOLOGY SEMINAR
The costs and benefits of SGLT2 inhibitors & GLP-1 RAs
The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.
“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.
Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”
“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”
According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.
Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.
“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.
Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”
“I have had very few of the ‘have nots’ who have been able to even consider these newer agents, which carry price tags of $600-$1,300 a month even with the availability of discounting coupons in the marketplace,” he added. “Most of these patients end up requiring a sulfonylurea or TZD [thiazolidinedione] as a second agent to achieve glycemic control. This makes it very difficult to achieve sufficient weight and metabolic control to avoid an eventual switch to insulin.”
Fatima Z. Syed, MD, an endocrine-trained general internist at DukeHealth in Durham, N.C., said she prescribes SGLT2 inhibitors and GLP-1 receptor agonists in combination with metformin. “I prescribe them frequently, but they are not first-line treatments,” she explained.
“Nothing replaces diet and exercise” as therapy for patients with type 2 diabetes, she added.
Neil S. Skolnik, MD, said that insurance companies were not preventing patients from using these drugs in his experience. He also provided an optimistic take on the accessibility of these drugs in the near future.
“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
The side effects
While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.
GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.
“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”
Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.
These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.
While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.
“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
The benefits
Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.
Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).
“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.
SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.
“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.
SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."
Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.
Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”
Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).
In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).
These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”
Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.
For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”
Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”
Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).
“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.
Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
The combination therapies
Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).
Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.
“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.
There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
What about adding insulin?
“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”
Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.
“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.
Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.
“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.
Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.
Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.
M. Alexander Otto contributed to this report.
The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.
“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.
Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”
“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”
According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.
Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.
“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.
Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”
“I have had very few of the ‘have nots’ who have been able to even consider these newer agents, which carry price tags of $600-$1,300 a month even with the availability of discounting coupons in the marketplace,” he added. “Most of these patients end up requiring a sulfonylurea or TZD [thiazolidinedione] as a second agent to achieve glycemic control. This makes it very difficult to achieve sufficient weight and metabolic control to avoid an eventual switch to insulin.”
Fatima Z. Syed, MD, an endocrine-trained general internist at DukeHealth in Durham, N.C., said she prescribes SGLT2 inhibitors and GLP-1 receptor agonists in combination with metformin. “I prescribe them frequently, but they are not first-line treatments,” she explained.
“Nothing replaces diet and exercise” as therapy for patients with type 2 diabetes, she added.
Neil S. Skolnik, MD, said that insurance companies were not preventing patients from using these drugs in his experience. He also provided an optimistic take on the accessibility of these drugs in the near future.
“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
The side effects
While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.
GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.
“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”
Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.
These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.
While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.
“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
The benefits
Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.
Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).
“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.
SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.
“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.
SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."
Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.
Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”
Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).
In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).
These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”
Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.
For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”
Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”
Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).
“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.
Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
The combination therapies
Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).
Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.
“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.
There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
What about adding insulin?
“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”
Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.
“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.
Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.
“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.
Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.
Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.
M. Alexander Otto contributed to this report.
The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.
“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.
Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”
“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”
According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.
Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.
“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.
Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”
“I have had very few of the ‘have nots’ who have been able to even consider these newer agents, which carry price tags of $600-$1,300 a month even with the availability of discounting coupons in the marketplace,” he added. “Most of these patients end up requiring a sulfonylurea or TZD [thiazolidinedione] as a second agent to achieve glycemic control. This makes it very difficult to achieve sufficient weight and metabolic control to avoid an eventual switch to insulin.”
Fatima Z. Syed, MD, an endocrine-trained general internist at DukeHealth in Durham, N.C., said she prescribes SGLT2 inhibitors and GLP-1 receptor agonists in combination with metformin. “I prescribe them frequently, but they are not first-line treatments,” she explained.
“Nothing replaces diet and exercise” as therapy for patients with type 2 diabetes, she added.
Neil S. Skolnik, MD, said that insurance companies were not preventing patients from using these drugs in his experience. He also provided an optimistic take on the accessibility of these drugs in the near future.
“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
The side effects
While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.
GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.
“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”
Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.
These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.
While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.
“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
The benefits
Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.
Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).
“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.
SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.
“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.
SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."
Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.
Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”
Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).
In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).
These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”
Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.
For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”
Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”
Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).
“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.
Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
The combination therapies
Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).
Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.
“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.
There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
What about adding insulin?
“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”
Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.
“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.
Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.
“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.
Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.
Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.
M. Alexander Otto contributed to this report.
SGLT2 inhibitors, GLP-1 RAs are effective, but costly in T2D
Polyester. Plywood. Pizza. Skin allergens lurk in unusual places
NEWPORT BEACH, CALIF. – , according to dermatologist Jennifer H. Perryman, MD.
Here’s a closer look at the allergens highlighted by Dr. Perryman in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar:
Formaldehyde: It’s everywhere
“In general, formaldehyde is found on everyone in this room in two different places: preservatives in skin care products and in a lot of our clothing,” said Dr. Perryman, who practices in Greeley and Fort Collins, Colo.
The preservative is used in an even wider variety of products, including fluids used in industry (such as metalworking) and topical medications. But people are especially likely to encounter it in clothing – via formaldehyde textile resins – as well as in cosmetics, soaps, and lotions.
On the clothing front, Dr. Perryman said, formaldehyde textile resins have been used since the 1930s. They’re used to treat blends of synthetic and cotton fibers and bed sheets. Beware of “wrinkle resistant” and “permanent press” clothing (although not all have been treated with this resin). “Newer formaldehyde textile resins have less formaldehyde release, but they may be more expensive, and some industries may not use them,” she said.
Avoiding formaldehyde textile resins isn’t a simple matter.” You have to go out of your way to stay away from a polyester-cotton blend,” she said. “And don’t forget bedsheets,” she added, noting that the packaging on some sheets include information about cotton count, “but when you flip over the label it says it’s ‘50% cotton and 50% polyester or other.’ ”
Some patients will bring their own bedsheets to hotels so they don’t experience flares from hotel bedsheets, she added.
Other products can trigger this skin allergy. Beware, Dr. Perryman said, of formaldehyde exposure from paper, cardboard, cigarette smoke, processed wood products like plywood, foam housing and industrial insulation, embalming fluid and tissue fixatives, and some paints and adhesives.
What are the signs that someone may have a case of formaldehyde allergy? It may cause patchy generalized dermatitis, erythroderma, and nummular dermatitis. It may spare the hands, feet, and face because those parts of the body have less exposure to clothing, and it’s likely to especially affect body areas where clothing is tight. And for unknown reasons, this allergy is more common in the elderly, Dr. Perryman said.
Textile dye: Beware polyester
This allergy is mainly triggered by synthetic fabrics like polyester, rayon, and acetate, she noted. Darker colors are more allergenic. Clothes made of natural fibers such as cotton, silk, linen, and wool are alternatives. These are not dyed with these dyes, she said, adding that a reaction to wool will be from irritation, not from the dye.
Paraphenylenediamine: Keep an eye out for this dye ingredient
Paraphenylenediamine, which can trigger allergic reactions, is found in leather dye, fur dye, and some (but not all) hair dyes. Be aware that it can cross-react with other allergens like sulfonamide medications.
If a patch test turns up a reaction to “Black-Rubber Mix,” which includes paraphenylenediamine, consider whether the patient has exposure to the rubber in tires. Car mechanics may be affected by this allergy, Dr. Perryman said.
Neomycin: A drop of trouble
Allergy to the antibiotic neomycin can be triggered by exposure to gentamicin and tobramycin eye drops. Patients may believe they have an infection, Dr. Perryman said, so consider getting a culture. In some cases, an allergic reaction to neomycin may be incorrectly diagnosed as cellulitis.
Nickel: Not just a jewelry hazard
Jewelry and coins can trigger nickel allergies, but be aware that systemic nickel allergy can also trigger skin problems from a patient’s diet. It may be necessary to put patients on a low-nickel diet that avoids foods such as healthy grains, greens (especially spinach), nuts, legumes, and chocolate. “I always feel bad” putting patients on a restrictive diet, Dr. Perryman said, but it can be helpful to take 500 mg of vitamin C three times a day since it binds to nickel.
Cobalt: Watch the chocolate and coffee
Jewelry with cobalt can cause an allergic reaction. Dr. Perryman tells patients to buy an inexpensive “spot test” product online that detects whether jewelry has nickel or cobalt. Cobalt allergy can also trigger symptoms in patients exposed to “hard metal” industrial tools, cement, and masonry. Workers in the plastics and dye industries may be exposed too.
Like nickel, Dr. Perryman said, systemic cobalt allergy related to diet is also possible. The list of foods that contain higher levels of cobalt is long, and includes apricots, beans, beer, chocolate, coffee, nuts, tea, and whole-grain flour.
Dr. Perryman also mentioned several other allergens to keep in mind:
- Chromate can trigger reactions in people who wear leather shoes (the metal can be used in tanning). It can also cause problems in workers exposed to it via cement, bricks, drywall, and metal plating.
- Chromium picolinate, an over-the-counter supplement, can cause systemic dermatitis.
- Gold in jewelry can trigger an allergic reaction. Talk to patients about replating their jewelry, Dr. Perryman said.
- Rubber can trigger reactions due to exposure to rubber bands, makeup sponges, and rubber gloves (even nitrile ones). Be aware that both rubber and latex allergies may coexist and consider a blood test for latex allergy.
- Systemic balsam allergy related to an individual’s diet is possible. Tomato is an especially big villain on this front, along with citrus fruits, spices, cola, chili, and chocolate.
Dr. Perryman disclosed consulting work for IntraDerm. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – , according to dermatologist Jennifer H. Perryman, MD.
Here’s a closer look at the allergens highlighted by Dr. Perryman in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar:
Formaldehyde: It’s everywhere
“In general, formaldehyde is found on everyone in this room in two different places: preservatives in skin care products and in a lot of our clothing,” said Dr. Perryman, who practices in Greeley and Fort Collins, Colo.
The preservative is used in an even wider variety of products, including fluids used in industry (such as metalworking) and topical medications. But people are especially likely to encounter it in clothing – via formaldehyde textile resins – as well as in cosmetics, soaps, and lotions.
On the clothing front, Dr. Perryman said, formaldehyde textile resins have been used since the 1930s. They’re used to treat blends of synthetic and cotton fibers and bed sheets. Beware of “wrinkle resistant” and “permanent press” clothing (although not all have been treated with this resin). “Newer formaldehyde textile resins have less formaldehyde release, but they may be more expensive, and some industries may not use them,” she said.
Avoiding formaldehyde textile resins isn’t a simple matter.” You have to go out of your way to stay away from a polyester-cotton blend,” she said. “And don’t forget bedsheets,” she added, noting that the packaging on some sheets include information about cotton count, “but when you flip over the label it says it’s ‘50% cotton and 50% polyester or other.’ ”
Some patients will bring their own bedsheets to hotels so they don’t experience flares from hotel bedsheets, she added.
Other products can trigger this skin allergy. Beware, Dr. Perryman said, of formaldehyde exposure from paper, cardboard, cigarette smoke, processed wood products like plywood, foam housing and industrial insulation, embalming fluid and tissue fixatives, and some paints and adhesives.
What are the signs that someone may have a case of formaldehyde allergy? It may cause patchy generalized dermatitis, erythroderma, and nummular dermatitis. It may spare the hands, feet, and face because those parts of the body have less exposure to clothing, and it’s likely to especially affect body areas where clothing is tight. And for unknown reasons, this allergy is more common in the elderly, Dr. Perryman said.
Textile dye: Beware polyester
This allergy is mainly triggered by synthetic fabrics like polyester, rayon, and acetate, she noted. Darker colors are more allergenic. Clothes made of natural fibers such as cotton, silk, linen, and wool are alternatives. These are not dyed with these dyes, she said, adding that a reaction to wool will be from irritation, not from the dye.
Paraphenylenediamine: Keep an eye out for this dye ingredient
Paraphenylenediamine, which can trigger allergic reactions, is found in leather dye, fur dye, and some (but not all) hair dyes. Be aware that it can cross-react with other allergens like sulfonamide medications.
If a patch test turns up a reaction to “Black-Rubber Mix,” which includes paraphenylenediamine, consider whether the patient has exposure to the rubber in tires. Car mechanics may be affected by this allergy, Dr. Perryman said.
Neomycin: A drop of trouble
Allergy to the antibiotic neomycin can be triggered by exposure to gentamicin and tobramycin eye drops. Patients may believe they have an infection, Dr. Perryman said, so consider getting a culture. In some cases, an allergic reaction to neomycin may be incorrectly diagnosed as cellulitis.
Nickel: Not just a jewelry hazard
Jewelry and coins can trigger nickel allergies, but be aware that systemic nickel allergy can also trigger skin problems from a patient’s diet. It may be necessary to put patients on a low-nickel diet that avoids foods such as healthy grains, greens (especially spinach), nuts, legumes, and chocolate. “I always feel bad” putting patients on a restrictive diet, Dr. Perryman said, but it can be helpful to take 500 mg of vitamin C three times a day since it binds to nickel.
Cobalt: Watch the chocolate and coffee
Jewelry with cobalt can cause an allergic reaction. Dr. Perryman tells patients to buy an inexpensive “spot test” product online that detects whether jewelry has nickel or cobalt. Cobalt allergy can also trigger symptoms in patients exposed to “hard metal” industrial tools, cement, and masonry. Workers in the plastics and dye industries may be exposed too.
Like nickel, Dr. Perryman said, systemic cobalt allergy related to diet is also possible. The list of foods that contain higher levels of cobalt is long, and includes apricots, beans, beer, chocolate, coffee, nuts, tea, and whole-grain flour.
Dr. Perryman also mentioned several other allergens to keep in mind:
- Chromate can trigger reactions in people who wear leather shoes (the metal can be used in tanning). It can also cause problems in workers exposed to it via cement, bricks, drywall, and metal plating.
- Chromium picolinate, an over-the-counter supplement, can cause systemic dermatitis.
- Gold in jewelry can trigger an allergic reaction. Talk to patients about replating their jewelry, Dr. Perryman said.
- Rubber can trigger reactions due to exposure to rubber bands, makeup sponges, and rubber gloves (even nitrile ones). Be aware that both rubber and latex allergies may coexist and consider a blood test for latex allergy.
- Systemic balsam allergy related to an individual’s diet is possible. Tomato is an especially big villain on this front, along with citrus fruits, spices, cola, chili, and chocolate.
Dr. Perryman disclosed consulting work for IntraDerm. SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – , according to dermatologist Jennifer H. Perryman, MD.
Here’s a closer look at the allergens highlighted by Dr. Perryman in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar:
Formaldehyde: It’s everywhere
“In general, formaldehyde is found on everyone in this room in two different places: preservatives in skin care products and in a lot of our clothing,” said Dr. Perryman, who practices in Greeley and Fort Collins, Colo.
The preservative is used in an even wider variety of products, including fluids used in industry (such as metalworking) and topical medications. But people are especially likely to encounter it in clothing – via formaldehyde textile resins – as well as in cosmetics, soaps, and lotions.
On the clothing front, Dr. Perryman said, formaldehyde textile resins have been used since the 1930s. They’re used to treat blends of synthetic and cotton fibers and bed sheets. Beware of “wrinkle resistant” and “permanent press” clothing (although not all have been treated with this resin). “Newer formaldehyde textile resins have less formaldehyde release, but they may be more expensive, and some industries may not use them,” she said.
Avoiding formaldehyde textile resins isn’t a simple matter.” You have to go out of your way to stay away from a polyester-cotton blend,” she said. “And don’t forget bedsheets,” she added, noting that the packaging on some sheets include information about cotton count, “but when you flip over the label it says it’s ‘50% cotton and 50% polyester or other.’ ”
Some patients will bring their own bedsheets to hotels so they don’t experience flares from hotel bedsheets, she added.
Other products can trigger this skin allergy. Beware, Dr. Perryman said, of formaldehyde exposure from paper, cardboard, cigarette smoke, processed wood products like plywood, foam housing and industrial insulation, embalming fluid and tissue fixatives, and some paints and adhesives.
What are the signs that someone may have a case of formaldehyde allergy? It may cause patchy generalized dermatitis, erythroderma, and nummular dermatitis. It may spare the hands, feet, and face because those parts of the body have less exposure to clothing, and it’s likely to especially affect body areas where clothing is tight. And for unknown reasons, this allergy is more common in the elderly, Dr. Perryman said.
Textile dye: Beware polyester
This allergy is mainly triggered by synthetic fabrics like polyester, rayon, and acetate, she noted. Darker colors are more allergenic. Clothes made of natural fibers such as cotton, silk, linen, and wool are alternatives. These are not dyed with these dyes, she said, adding that a reaction to wool will be from irritation, not from the dye.
Paraphenylenediamine: Keep an eye out for this dye ingredient
Paraphenylenediamine, which can trigger allergic reactions, is found in leather dye, fur dye, and some (but not all) hair dyes. Be aware that it can cross-react with other allergens like sulfonamide medications.
If a patch test turns up a reaction to “Black-Rubber Mix,” which includes paraphenylenediamine, consider whether the patient has exposure to the rubber in tires. Car mechanics may be affected by this allergy, Dr. Perryman said.
Neomycin: A drop of trouble
Allergy to the antibiotic neomycin can be triggered by exposure to gentamicin and tobramycin eye drops. Patients may believe they have an infection, Dr. Perryman said, so consider getting a culture. In some cases, an allergic reaction to neomycin may be incorrectly diagnosed as cellulitis.
Nickel: Not just a jewelry hazard
Jewelry and coins can trigger nickel allergies, but be aware that systemic nickel allergy can also trigger skin problems from a patient’s diet. It may be necessary to put patients on a low-nickel diet that avoids foods such as healthy grains, greens (especially spinach), nuts, legumes, and chocolate. “I always feel bad” putting patients on a restrictive diet, Dr. Perryman said, but it can be helpful to take 500 mg of vitamin C three times a day since it binds to nickel.
Cobalt: Watch the chocolate and coffee
Jewelry with cobalt can cause an allergic reaction. Dr. Perryman tells patients to buy an inexpensive “spot test” product online that detects whether jewelry has nickel or cobalt. Cobalt allergy can also trigger symptoms in patients exposed to “hard metal” industrial tools, cement, and masonry. Workers in the plastics and dye industries may be exposed too.
Like nickel, Dr. Perryman said, systemic cobalt allergy related to diet is also possible. The list of foods that contain higher levels of cobalt is long, and includes apricots, beans, beer, chocolate, coffee, nuts, tea, and whole-grain flour.
Dr. Perryman also mentioned several other allergens to keep in mind:
- Chromate can trigger reactions in people who wear leather shoes (the metal can be used in tanning). It can also cause problems in workers exposed to it via cement, bricks, drywall, and metal plating.
- Chromium picolinate, an over-the-counter supplement, can cause systemic dermatitis.
- Gold in jewelry can trigger an allergic reaction. Talk to patients about replating their jewelry, Dr. Perryman said.
- Rubber can trigger reactions due to exposure to rubber bands, makeup sponges, and rubber gloves (even nitrile ones). Be aware that both rubber and latex allergies may coexist and consider a blood test for latex allergy.
- Systemic balsam allergy related to an individual’s diet is possible. Tomato is an especially big villain on this front, along with citrus fruits, spices, cola, chili, and chocolate.
Dr. Perryman disclosed consulting work for IntraDerm. SDEF and this news organization are owned by the same parent company.
REPORTING FROM SDEF WOMEN’S & PEDIATRIC DERMATOLOGY SEMINAR
Acne in women: What new insights tell us
NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.
she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.
About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”
Dr. Stein Gold offered these tips about treatment in this group of patients:
Inflammation
Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.
Oral contraceptives (OCs)
OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).
Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.
There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
Spironolactone
This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.
Truncal acne
Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.
“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”
Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).
SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.
she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.
About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”
Dr. Stein Gold offered these tips about treatment in this group of patients:
Inflammation
Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.
Oral contraceptives (OCs)
OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).
Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.
There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
Spironolactone
This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.
Truncal acne
Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.
“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”
Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).
SDEF and this news organization are owned by the same parent company.
NEWPORT BEACH, CALIF. – When it comes to acne in adult women, look past the jawline, beyond traditional medications, and toward greater control. That’s the message of a dermatologist who spoke at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.
“We should be aiming to get our patients to clear or almost clear, and we have the tools necessary to help that happen,” said Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.
she noted. Acne appears to affect 51% of women aged 20-29 years, she said, and prevalence dips to 15% in women older than 50 years.
About 80% of cases continue from adolescence, compared with about 20% that are new-onset during adulthood, she said. According to studies, she added, “most adult women have acne on multiple different areas of their face, not just the jawline. It’s similar to what we see in the adolescent population.”
Dr. Stein Gold offered these tips about treatment in this group of patients:
Inflammation
Researchers now consider that “all acne is inflammatory acne.” Be aggressive with anti-inflammatory treatment, and “continue even after the lesion is resolved” if needed to prevent scarring.
Oral contraceptives (OCs)
OCs can be helpful, but “we have to proceed with caution,” she said. A 2012 Cochrane Library review of 31 trials found that six combination OCs (COCs) “evaluated in placebo-controlled trials are effective in reducing inflammatory and noninflammatory facial acne lesions. Few important and consistent differences were found between COC types in their effectiveness for treating acne,” the review concluded (Cochrane Database Syst Rev. 2012 Jul 11;[7]:CD004425).
Results take time, however, and it “can take 3 months to see an effect, and 6 months for full effect,” Dr. Stein Gold noted.
There are multiple contraindications to the use of OCs, and they’ve been linked – controversially – to an increased risk of blood clots and breast cancer. However, risk of thrombosis also spikes – to significantly higher levels than with OC use – during pregnancy and the postpartum period, she said.
Spironolactone
This antihypertensive drug can be helpful, Dr. Stein Gold noted, although the one study in a 2009 Cochrane review that had acne as an outcome failed to find evidence of efficacy versus placebo (Cochrane Database Syst Rev. 2009 Apr 15;[2]:CD000194). Be aware of the boxed warning about links to cancer in rat studies, and consider the risk of potassium elevation in certain populations, she added. Watch the dose: fewer side effects are seen at 50-100 mg daily, although they’re still common, and it can take 3 months or more for improvements to appear, she said.
Truncal acne
Patients may be hesitant to mention they have acne on their chest and back. “They may not tell you about it, and you may not ask about it but [some patients] expect you to know about it and treat it,” Dr. Stein Gold said. She referred to trifarotene, a topical retinoid cream that, although not yet approved, appears to be safe and effective in treating acne on the face and trunk in phase 3 studies.
“Some people will say the trunk will get too irritated if you put a retinoid on it. But it absolutely can be used on the chest and back. The first thing I say to my patients is to expect to have redness and scaling for first 2 weeks. People pay money for that. It’s a chemical peel! It’s okay to have some sloughing; use an oil-free moisturizer.”
Dr. Stein Gold disclosed relationships with Galderma, Foamix, and Sol Gel (investigator, consultant); Valeant (consultant, speaker); and Dermira (investigator, speaker).
SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF WOMEN’S & PEDIATRIC DERMATOLOGY SEMINAR
Metformin linked to lower dementia risk in black patients
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
FROM ANNALS OF FAMILY MEDICINE
Key clinical point:
Major finding: Metformin monotherapy, compared with sulfonylurea monotherapy, was linked to a significantly lower risk for dementia in black patients (HR, 0.73; 95% CI, 0.6-0.89), but not in white patients (HR, 0.96; 95% CI, 0.9-1.03; P = .008).
Study details: Retrospective analysis of 73,761 patients aged 50 years or older in the Veterans Health Administration system who were tracked from 2000-2001 to 2015 and began metformin or sulfonylurea monotherapy after baseline.
Disclosures: The National Institutes of Health funded the study. The authors report no relevant disclosures.
Source: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
SGLT2 inhibitors for type 1 diabetes: Doctors debate the merits
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
EXPERT ANALYSIS FROM ADA 2019
New findings cast more doubt on ‘fat-but-fit’ theory
SAN FRANCISCO – Can you be “fat but fit” if you’re obese but don’t suffer from metabolic syndrome? Some advocates have claimed you can, but new findings presented at the annual scientific sessions of the American Diabetes Association provide more evidence that those extra pounds translate to extra cardiac risk.
Fat-but-fit is a misnomer, Yvonne Commodore-Mensah, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, said in an interview. “The metabolically healthy obese are not so healthy. [We found] they had a higher risk of heart disease than people who were metabolically healthy and nonobese.”
Studies began supporting the fat-but-fit “paradox” in the late 1990s. They showed “that all-cause and CVD [cardiovascular] mortality risk in obese individuals, as defined by body mass index (BMI), body fat percentage, or waist circumference, who are fit (i.e., cardiorespiratory fitness level above the age-specific and sex-specific 20th percentile) is not significantly different from their normal-weight and fit counterparts” (Br J Sports Med. 2018;52[3]:151-3).
However, a 2017 study had found that “metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure [compared with] normal weight, metabolically healthy individuals” (J Am Coll Cardiol. 2017;70[12]:1429-37). And a 2016 meta-analysis of 22 studies had produced similar results but also found that metabolically healthy obese individuals were better off, cardiac-health–wise, than those of normal weight who were metabolically unhealthy (Eur J Prev Cardiol. 2016;23[9]:956-66).
Dr. Commodore-Mensah and colleagues sought to establish through their study whether there was evidence of subclinical heart disease in people who are considered obese but metabolically healthy (Abstract 272-OR).
They tracked 11,884 participants in the Atherosclerosis Risk in Communities Study (ARIC) from 1990-1992 to 2016-2018. The study, which continues today, includes participants in suburban Minneapolis; Jackson, Miss.; Forsyth County, N.C.; and Washington County, Md.
None of the participants had previous cardiovascular disease at baseline (1990-1992). The researchers divided the participants into four groups at baseline: Nonobese (with metabolic syndrome, 20% of the total number of participants; or without metabolic syndrome, 51%) and obese (with metabolic syndrome, 20%; or without metabolic syndrome, 9%).
The average age range in the groups was 56-57 years. The percentage of women in the groups ranged from 53% to 58%, except for the obese and metabolically healthy group (73%). The percentage of black participants in the groups ranged from 17% (nonobese, metabolically unhealthy) to 45% (obese, metabolically healthy).
“People who were younger, women, and black were more likely to be classified as metabolically healthy obese,” Dr. Commodore-Mensah said.
According to one adjusted model with a median follow-up of 16 years and a total of 3,560 events, obese participants had a higher risk of incident cardiovascular disease, compared with their nonobese counterparts, regardless of whether they had metabolic syndrome.
When compared with the nonobese, metabolically healthy group, the risk grew in the nonobese, metabolically unhealthy group (hazard ratio, .24; 95% confidence interval, 1.12-1.36), as well as in the obese, metabolically healthy (HR, 1.33; 95% CI, 1.15-1.53) and the obese, metabolically unhealthy (HR, 2.11; 95% CI, 1.90-2.35) groups.
The researchers also focused on the cardiac biomarker known as high-sensitive cardiac troponin T (hs-cTnT), which indicates chronic myocardial damage. “This biomarker provides us with a window to the heart,” Dr. Commodore-Mensah said.
According to previous findings reported in 2014, ARIC participants who had hs-cTnT levels of 14 ng/L or higher were much more likely than were those with undetectable levels to suffer from heart failure, death from any cause, and coronary heart disease (JACC Heart Fail. 2014;2[6]:600-7).
Based on an analysis of the hs-cTnT levels in the present study, the researchers believe obese, metabolically healthy participants fell in the intermediate range of excess subclinical myocardial damage, between the nonobese and the obese participants who are also metabolically unhealthy.
“This group is not protected from heart disease,” Dr. Commodore-Mensah said. “They should be targeted, and they would benefit from behavioral changes, such as modifying their diet and increasing physical activity levels.”
The study is funded by the National Institutes of Health. Dr. Commodore-Mensah and six coauthors reported no relevant disclosures. Two coauthors reported various disclosures.
SAN FRANCISCO – Can you be “fat but fit” if you’re obese but don’t suffer from metabolic syndrome? Some advocates have claimed you can, but new findings presented at the annual scientific sessions of the American Diabetes Association provide more evidence that those extra pounds translate to extra cardiac risk.
Fat-but-fit is a misnomer, Yvonne Commodore-Mensah, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, said in an interview. “The metabolically healthy obese are not so healthy. [We found] they had a higher risk of heart disease than people who were metabolically healthy and nonobese.”
Studies began supporting the fat-but-fit “paradox” in the late 1990s. They showed “that all-cause and CVD [cardiovascular] mortality risk in obese individuals, as defined by body mass index (BMI), body fat percentage, or waist circumference, who are fit (i.e., cardiorespiratory fitness level above the age-specific and sex-specific 20th percentile) is not significantly different from their normal-weight and fit counterparts” (Br J Sports Med. 2018;52[3]:151-3).
However, a 2017 study had found that “metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure [compared with] normal weight, metabolically healthy individuals” (J Am Coll Cardiol. 2017;70[12]:1429-37). And a 2016 meta-analysis of 22 studies had produced similar results but also found that metabolically healthy obese individuals were better off, cardiac-health–wise, than those of normal weight who were metabolically unhealthy (Eur J Prev Cardiol. 2016;23[9]:956-66).
Dr. Commodore-Mensah and colleagues sought to establish through their study whether there was evidence of subclinical heart disease in people who are considered obese but metabolically healthy (Abstract 272-OR).
They tracked 11,884 participants in the Atherosclerosis Risk in Communities Study (ARIC) from 1990-1992 to 2016-2018. The study, which continues today, includes participants in suburban Minneapolis; Jackson, Miss.; Forsyth County, N.C.; and Washington County, Md.
None of the participants had previous cardiovascular disease at baseline (1990-1992). The researchers divided the participants into four groups at baseline: Nonobese (with metabolic syndrome, 20% of the total number of participants; or without metabolic syndrome, 51%) and obese (with metabolic syndrome, 20%; or without metabolic syndrome, 9%).
The average age range in the groups was 56-57 years. The percentage of women in the groups ranged from 53% to 58%, except for the obese and metabolically healthy group (73%). The percentage of black participants in the groups ranged from 17% (nonobese, metabolically unhealthy) to 45% (obese, metabolically healthy).
“People who were younger, women, and black were more likely to be classified as metabolically healthy obese,” Dr. Commodore-Mensah said.
According to one adjusted model with a median follow-up of 16 years and a total of 3,560 events, obese participants had a higher risk of incident cardiovascular disease, compared with their nonobese counterparts, regardless of whether they had metabolic syndrome.
When compared with the nonobese, metabolically healthy group, the risk grew in the nonobese, metabolically unhealthy group (hazard ratio, .24; 95% confidence interval, 1.12-1.36), as well as in the obese, metabolically healthy (HR, 1.33; 95% CI, 1.15-1.53) and the obese, metabolically unhealthy (HR, 2.11; 95% CI, 1.90-2.35) groups.
The researchers also focused on the cardiac biomarker known as high-sensitive cardiac troponin T (hs-cTnT), which indicates chronic myocardial damage. “This biomarker provides us with a window to the heart,” Dr. Commodore-Mensah said.
According to previous findings reported in 2014, ARIC participants who had hs-cTnT levels of 14 ng/L or higher were much more likely than were those with undetectable levels to suffer from heart failure, death from any cause, and coronary heart disease (JACC Heart Fail. 2014;2[6]:600-7).
Based on an analysis of the hs-cTnT levels in the present study, the researchers believe obese, metabolically healthy participants fell in the intermediate range of excess subclinical myocardial damage, between the nonobese and the obese participants who are also metabolically unhealthy.
“This group is not protected from heart disease,” Dr. Commodore-Mensah said. “They should be targeted, and they would benefit from behavioral changes, such as modifying their diet and increasing physical activity levels.”
The study is funded by the National Institutes of Health. Dr. Commodore-Mensah and six coauthors reported no relevant disclosures. Two coauthors reported various disclosures.
SAN FRANCISCO – Can you be “fat but fit” if you’re obese but don’t suffer from metabolic syndrome? Some advocates have claimed you can, but new findings presented at the annual scientific sessions of the American Diabetes Association provide more evidence that those extra pounds translate to extra cardiac risk.
Fat-but-fit is a misnomer, Yvonne Commodore-Mensah, PhD, RN, assistant professor at Johns Hopkins School of Nursing, Baltimore, said in an interview. “The metabolically healthy obese are not so healthy. [We found] they had a higher risk of heart disease than people who were metabolically healthy and nonobese.”
Studies began supporting the fat-but-fit “paradox” in the late 1990s. They showed “that all-cause and CVD [cardiovascular] mortality risk in obese individuals, as defined by body mass index (BMI), body fat percentage, or waist circumference, who are fit (i.e., cardiorespiratory fitness level above the age-specific and sex-specific 20th percentile) is not significantly different from their normal-weight and fit counterparts” (Br J Sports Med. 2018;52[3]:151-3).
However, a 2017 study had found that “metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure [compared with] normal weight, metabolically healthy individuals” (J Am Coll Cardiol. 2017;70[12]:1429-37). And a 2016 meta-analysis of 22 studies had produced similar results but also found that metabolically healthy obese individuals were better off, cardiac-health–wise, than those of normal weight who were metabolically unhealthy (Eur J Prev Cardiol. 2016;23[9]:956-66).
Dr. Commodore-Mensah and colleagues sought to establish through their study whether there was evidence of subclinical heart disease in people who are considered obese but metabolically healthy (Abstract 272-OR).
They tracked 11,884 participants in the Atherosclerosis Risk in Communities Study (ARIC) from 1990-1992 to 2016-2018. The study, which continues today, includes participants in suburban Minneapolis; Jackson, Miss.; Forsyth County, N.C.; and Washington County, Md.
None of the participants had previous cardiovascular disease at baseline (1990-1992). The researchers divided the participants into four groups at baseline: Nonobese (with metabolic syndrome, 20% of the total number of participants; or without metabolic syndrome, 51%) and obese (with metabolic syndrome, 20%; or without metabolic syndrome, 9%).
The average age range in the groups was 56-57 years. The percentage of women in the groups ranged from 53% to 58%, except for the obese and metabolically healthy group (73%). The percentage of black participants in the groups ranged from 17% (nonobese, metabolically unhealthy) to 45% (obese, metabolically healthy).
“People who were younger, women, and black were more likely to be classified as metabolically healthy obese,” Dr. Commodore-Mensah said.
According to one adjusted model with a median follow-up of 16 years and a total of 3,560 events, obese participants had a higher risk of incident cardiovascular disease, compared with their nonobese counterparts, regardless of whether they had metabolic syndrome.
When compared with the nonobese, metabolically healthy group, the risk grew in the nonobese, metabolically unhealthy group (hazard ratio, .24; 95% confidence interval, 1.12-1.36), as well as in the obese, metabolically healthy (HR, 1.33; 95% CI, 1.15-1.53) and the obese, metabolically unhealthy (HR, 2.11; 95% CI, 1.90-2.35) groups.
The researchers also focused on the cardiac biomarker known as high-sensitive cardiac troponin T (hs-cTnT), which indicates chronic myocardial damage. “This biomarker provides us with a window to the heart,” Dr. Commodore-Mensah said.
According to previous findings reported in 2014, ARIC participants who had hs-cTnT levels of 14 ng/L or higher were much more likely than were those with undetectable levels to suffer from heart failure, death from any cause, and coronary heart disease (JACC Heart Fail. 2014;2[6]:600-7).
Based on an analysis of the hs-cTnT levels in the present study, the researchers believe obese, metabolically healthy participants fell in the intermediate range of excess subclinical myocardial damage, between the nonobese and the obese participants who are also metabolically unhealthy.
“This group is not protected from heart disease,” Dr. Commodore-Mensah said. “They should be targeted, and they would benefit from behavioral changes, such as modifying their diet and increasing physical activity levels.”
The study is funded by the National Institutes of Health. Dr. Commodore-Mensah and six coauthors reported no relevant disclosures. Two coauthors reported various disclosures.
REPORTING FROM ADA 2019
To help patients stay on diabetes regimens: Communicate, educate, and use technology
SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office).
Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.
“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”
According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).
Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).
Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.
Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).
Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:
- Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
- Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
- Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
- Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
- Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
- Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.
And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.
Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.
SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office).
Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.
“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”
According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).
Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).
Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.
Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).
Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:
- Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
- Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
- Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
- Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
- Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
- Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.
And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.
Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.
SAN FRANCISCO – Are you having trouble helping patients take their diabetes medications as directed? Try installing 32-inch screens in the examination rooms for a lab result show-and-tell. Keep pharmaceutical marketers out of your hair (and office).
Those are among the suggestions offered by two physicians during a symposium on drug adherence at the annual scientific sessions of the American Diabetes Association.
“Nonadherence is not a case of patients being bad,” said internist and researcher Niteesh K. Choudhry, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston. “When half of your patients are nonadherent, I can guarantee you [they] aren’t trying to hurt themselves.”
According to Dr. Choudhry’s own research published in 2011 and based on 2008 data, about 25% of patients do not fill prescriptions after leaving their doctors’ offices. That level for diabetes medications – 42% of patients – is especially high (Am J Med. 2011;124[11]:1081.e9-22).
Other findings, he said, have suggested that half of patients fail to adhere to evidence-based prescribed regimens over the long term. And three groups have especially low levels of adherence: people of color, women, and patients who are caregivers (possibly because they are too busy caring for others to care for themselves).
Various factors affect adherence, including forgetfulness, drug interactions or side effects, and the different colors and shapes of pills. The latter can confuse patients because colors and shapes may be different from prescription to prescription even for the same medication, he said.
Dr. Choudhry added that there’s another factor: multiple prescriptions from multiple physicians that require multiple pharmacy visits. His findings suggest that adherence improves when prescriptions are consolidated to limit the need to visit the drugstore. “The chaos of our health care system leads to nonadherence,” he said (Arch Intern Med. 2011;171[9]:814-22).
Internist Lawrence Garber, MD, of Reliant Medical Group in Worcester, Mass., offered these tips about boosting drug adherence:
- Develop trust with patients. “They need to trust that I’m their advocate, and that they’re my No. 1 reason for prescribing the medication, and not making myself more money,” he said.
- Provide educational resources. “We give them resources online. If their EHR [electronic health record] identifies that they’re diabetic, then they get information about diabetes printed out.”
- Use technology to promote messages about diabetes. Dr. Garber said his clinic has installed screens in the examination rooms so that he can show patients their data. “It [makes it] very clear for them to see why what they’re doing now is not working,’’ and why there is a need to change to a different regimen. In addition, screens in the waiting room can display educational slides about diabetes.
- Set up clinic-wide medication protocols. “We’ve set up protocols and pathways for diabetes, hypertension, and high cholesterol to make it easy to prescribe medications that are lower cost and to make sure we’re following the same path,” Dr. Garber said.
- Stay independent. “I haven’t seen a drug rep in decades. It’s an organizational policy that we don’t see them, so we’re less likely to be biased.”
- Make it easier for patients to take medications. Dr. Garber urged colleagues to talk to their patients about using strategies such as printed pill schedules, weekly pill organizers, auto refills, and smartphone alarm reminders to facilitate adherence.
And, he said, you may wish to make it clear that you will check on whether prescriptions are filled. That way, “the patients know that you’re looking,” and it can actually lead to improved adherence.
Dr. Choudhry reported that his research has been funded by unrestricted grants to his institution from insurers, government funders, nonprofit foundations, pharmaceutical companies (including Merck, Sanofi, and Astra Zeneca), and device makers (including Medisafe). Dr. Garber reported no relevant disclosures.
REPORTING FROM ADA 2019