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Don’t miss type 1 diabetes in adults
Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.
New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.
Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”
In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.
Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.
Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.
Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.
“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.
The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.
“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.
The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.
Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.
New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.
Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”
In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.
Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.
Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.
Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.
“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.
The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.
“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.
The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.
Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.
New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.
Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”
In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.
Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.
Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.
Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.
“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.
The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.
“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.
The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.
FROM ANNALS OF INTERNAL MEDICINE
Are vitamin D levels key to canagliflozin’s fracture risk?
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Tirzepatide superior to semaglutide for A1c control, weight loss
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EASD 2023
Echocardiography boosts prognostic power in T1D
AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.
Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.
The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.
Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
‘Trying to figure out’ the type 1 diabetes link
“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.
The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.
The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.
This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.
Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
MPI reflects left ventricular function
MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.
“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”
The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.
The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.
Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.
The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.
Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
‘Trying to figure out’ the type 1 diabetes link
“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.
The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.
The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.
This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.
Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
MPI reflects left ventricular function
MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.
“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”
The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.
The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.
Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.
The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.
Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
‘Trying to figure out’ the type 1 diabetes link
“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.
The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.
The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.
This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.
Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
MPI reflects left ventricular function
MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.
“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”
The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.
The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT ESC 2023
FDA panel rejects implanted GLP1-RA dosing device for T2D
Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Exercise timing may dictate obesity, type 2 diabetes risk
Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.
The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.
For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.
However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.
Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
Morning exercisers perform less physical activity
Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”
The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.
They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.
The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).
The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.
Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).
Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).
Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).
Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).
The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.
“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.
However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.
“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
No association between evening activity and type 2 diabetes risk
In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.
The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.
After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.
However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).
The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.
Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.
The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.
For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.
However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.
Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
Morning exercisers perform less physical activity
Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”
The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.
They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.
The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).
The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.
Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).
Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).
Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).
Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).
The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.
“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.
However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.
“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
No association between evening activity and type 2 diabetes risk
In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.
The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.
After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.
However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).
The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.
Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.
The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.
For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.
However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.
Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
Morning exercisers perform less physical activity
Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”
The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.
They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.
The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).
The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.
Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).
Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).
Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).
Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).
The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.
“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.
However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.
“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
No association between evening activity and type 2 diabetes risk
In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.
The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.
After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.
However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).
The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.
Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
Beyond A1c: Implementing the new ESC 2023 guidelines
A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.
Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.
Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.
The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.
Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.
Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.
For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.
There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.
Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.
The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.
The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.
For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.
Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.
Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.
Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.
In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.
Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.
A version of this article appeared on Medscape.com.
A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.
Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.
Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.
The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.
Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.
Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.
For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.
There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.
Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.
The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.
The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.
For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.
Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.
Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.
Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.
In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.
Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.
A version of this article appeared on Medscape.com.
A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.
Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.
Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.
The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.
Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.
Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.
For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.
There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.
Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.
The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.
The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.
For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.
Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.
Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.
Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.
In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.
Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.
A version of this article appeared on Medscape.com.
Islet, kidney transplants boost survival in type 1 diabetes
TOPLINE:
.
METHODOLOGY:
- Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
- Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
- The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.
TAKEAWAY:
- Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
- Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
- At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.
IN PRACTICE:
“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”
SOURCE:
Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).
LIMITATIONS:
Observational, potential for residual confounding.
DISCLOSURES:
Dr. Maanaoui reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
- Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
- The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.
TAKEAWAY:
- Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
- Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
- At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.
IN PRACTICE:
“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”
SOURCE:
Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).
LIMITATIONS:
Observational, potential for residual confounding.
DISCLOSURES:
Dr. Maanaoui reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
- Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
- The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.
TAKEAWAY:
- Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
- Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
- At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.
IN PRACTICE:
“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”
SOURCE:
Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).
LIMITATIONS:
Observational, potential for residual confounding.
DISCLOSURES:
Dr. Maanaoui reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AAP advises against low-carb diets for children with diabetes
according to a new clinical report.
Citing a lack of high-quality data and potential for adverse effects with carbohydrate restriction among younger individuals, lead author Anna Neyman, MD, of Indiana University, Indianapolis, and colleagues suggested that pediatric patients with type 2 diabetes should focus on reducing nutrient-poor carbohydrate intake, while those with type 1 diabetes should only pursue broader carbohydrate restriction under close medical supervision.
“There are no guidelines for restricting dietary carbohydrate consumption to reduce risk for diabetes or improve diabetes outcomes in youth,” the investigators wrote in Pediatrics. “Thus, there is a need to provide practical recommendations for pediatricians regarding the use of low-carbohydrate diets in patients who elect to follow these diets, including those with type 1 diabetes and for patients with obesity, prediabetes, and type 2 diabetes.”
Their new report includes a summary of the various types of carbohydrate-restricted diets, a review of available evidence for these diets among pediatric patients with type 1 and type 2 diabetes, and several practical recommendations based on their findings.
Dr. Neyman and colleagues first noted a lack of standardization in describing the various tiers of carbohydrate restriction; however, they offered some rough guidelines. Compared with a typical, balanced diet, which includes 45%-65% of calories from carbohydrates, a moderately restrictive diet includes 26%-44% of calories from carbohydrates, while a low-carb diet includes less than 26% of calories from carbs. Further down the scale, very low-carb diets and ketogenic diets call for 20-50 g of carbs per day or less than 20 g of carbs per day, respectively.
“There is evidence from adult studies that these diets can be associated with significant weight loss, reduction in insulin levels or insulin requirements, and improvement in glucose control,” the investigators noted. “Nevertheless, there is a lack of long-term safety and efficacy outcomes in youth.”
They went on to cite a range of safety concerns, including “growth deceleration, nutritional deficiencies, poor bone health, nutritional ketosis that cannot be distinguished from ketosis resulting from insulin deficiency, and disordered eating behaviors.”
“Body dissatisfaction associated with restrictive dieting practices places children and adolescents at risk for inadequate dietary intake, excessive weight gain resulting from binge-eating after restricting food intake, and use of harmful weight-control strategies,” the investigators wrote. “Moreover, restrictive dieting practices may negatively impact mental health and self-concept and are directly associated with decreased mood and increased feelings of anxiety.”
Until more evidence is available, Dr. Neyman and colleagues advised adherence to a balanced diet, including increased dietary fiber and reduced consumption of ultra-processed carbohydrates.
“Eliminating sugary beverages and juices significantly improves blood glucose and weight management in children and adolescents,” they noted.
For pediatric patients with type 1 diabetes, the investigators suggested that low-carb and very low-carb diets should only be pursued “under close diabetes care team supervision utilizing safety guidelines.”
Lack of evidence is the problem
David Ludwig, MD, PhD, codirector of the New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, and professor of pediatrics at Harvard Medical School, also in Boston, said the review is “rather general” and “reiterates common, although not always fair, concerns about carbohydrate restriction.”
“The main issue they highlight is the lack of evidence, especially from clinical trials, for a low-carbohydrate diet in children, as related to diabetes,” Dr. Ludwig said in a written comment, noting that this is indeed an issue. “However, what needs to be recognized is that a conventional high-carbohydrate diet has never been shown to be superior in adults or children for diabetes. Furthermore, whereas a poorly formulated low-carb diet may have adverse effects and risks (e.g., nutrient deficiencies), so can a high-carbohydrate diet – including an increase in triglycerides and other risk factors comprising metabolic syndrome.”
He said that the “main challenge in diabetes is to control blood glucose after eating,” and a high-carb makes this more difficult, as it requires more insulin after a meal than a low-carb meal would require, and increases risk of subsequent hypoglycemia.
For those interested in an alternative perspective to the AAP clinical report, Dr. Ludwig recommended two of his recent review articles, including one published in the Journal of Nutrition and another from the Journal of Clinical Investigation. In both, notes the long history of carbohydrate restriction for patients with diabetes, with usage dating back to the 1700s. Although the diet fell out of favor with the introduction of insulin, Dr. Ludwig believes that it needs to be reconsidered, and is more than a passing fad.
“Preliminary research suggests that this dietary approach might transform clinical management and perhaps normalize HbA1c for many people with diabetes, at substantially reduced treatment costs,” Dr. Ludwig and colleagues wrote in the JCI review. “High-quality randomized controlled trials, with intensive support for behavior changes, will be needed to address this possibility and assess long-term safety and sustainability. With total medical costs of diabetes in the United States approaching $1 billion a day, this research must assume high priority.”
This clinical report was commissioned by the AAP. Dr. Ludwig received royalties for books that recommend a carbohydrate-modified diet.
This article was updated 9/20/23.
according to a new clinical report.
Citing a lack of high-quality data and potential for adverse effects with carbohydrate restriction among younger individuals, lead author Anna Neyman, MD, of Indiana University, Indianapolis, and colleagues suggested that pediatric patients with type 2 diabetes should focus on reducing nutrient-poor carbohydrate intake, while those with type 1 diabetes should only pursue broader carbohydrate restriction under close medical supervision.
“There are no guidelines for restricting dietary carbohydrate consumption to reduce risk for diabetes or improve diabetes outcomes in youth,” the investigators wrote in Pediatrics. “Thus, there is a need to provide practical recommendations for pediatricians regarding the use of low-carbohydrate diets in patients who elect to follow these diets, including those with type 1 diabetes and for patients with obesity, prediabetes, and type 2 diabetes.”
Their new report includes a summary of the various types of carbohydrate-restricted diets, a review of available evidence for these diets among pediatric patients with type 1 and type 2 diabetes, and several practical recommendations based on their findings.
Dr. Neyman and colleagues first noted a lack of standardization in describing the various tiers of carbohydrate restriction; however, they offered some rough guidelines. Compared with a typical, balanced diet, which includes 45%-65% of calories from carbohydrates, a moderately restrictive diet includes 26%-44% of calories from carbohydrates, while a low-carb diet includes less than 26% of calories from carbs. Further down the scale, very low-carb diets and ketogenic diets call for 20-50 g of carbs per day or less than 20 g of carbs per day, respectively.
“There is evidence from adult studies that these diets can be associated with significant weight loss, reduction in insulin levels or insulin requirements, and improvement in glucose control,” the investigators noted. “Nevertheless, there is a lack of long-term safety and efficacy outcomes in youth.”
They went on to cite a range of safety concerns, including “growth deceleration, nutritional deficiencies, poor bone health, nutritional ketosis that cannot be distinguished from ketosis resulting from insulin deficiency, and disordered eating behaviors.”
“Body dissatisfaction associated with restrictive dieting practices places children and adolescents at risk for inadequate dietary intake, excessive weight gain resulting from binge-eating after restricting food intake, and use of harmful weight-control strategies,” the investigators wrote. “Moreover, restrictive dieting practices may negatively impact mental health and self-concept and are directly associated with decreased mood and increased feelings of anxiety.”
Until more evidence is available, Dr. Neyman and colleagues advised adherence to a balanced diet, including increased dietary fiber and reduced consumption of ultra-processed carbohydrates.
“Eliminating sugary beverages and juices significantly improves blood glucose and weight management in children and adolescents,” they noted.
For pediatric patients with type 1 diabetes, the investigators suggested that low-carb and very low-carb diets should only be pursued “under close diabetes care team supervision utilizing safety guidelines.”
Lack of evidence is the problem
David Ludwig, MD, PhD, codirector of the New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, and professor of pediatrics at Harvard Medical School, also in Boston, said the review is “rather general” and “reiterates common, although not always fair, concerns about carbohydrate restriction.”
“The main issue they highlight is the lack of evidence, especially from clinical trials, for a low-carbohydrate diet in children, as related to diabetes,” Dr. Ludwig said in a written comment, noting that this is indeed an issue. “However, what needs to be recognized is that a conventional high-carbohydrate diet has never been shown to be superior in adults or children for diabetes. Furthermore, whereas a poorly formulated low-carb diet may have adverse effects and risks (e.g., nutrient deficiencies), so can a high-carbohydrate diet – including an increase in triglycerides and other risk factors comprising metabolic syndrome.”
He said that the “main challenge in diabetes is to control blood glucose after eating,” and a high-carb makes this more difficult, as it requires more insulin after a meal than a low-carb meal would require, and increases risk of subsequent hypoglycemia.
For those interested in an alternative perspective to the AAP clinical report, Dr. Ludwig recommended two of his recent review articles, including one published in the Journal of Nutrition and another from the Journal of Clinical Investigation. In both, notes the long history of carbohydrate restriction for patients with diabetes, with usage dating back to the 1700s. Although the diet fell out of favor with the introduction of insulin, Dr. Ludwig believes that it needs to be reconsidered, and is more than a passing fad.
“Preliminary research suggests that this dietary approach might transform clinical management and perhaps normalize HbA1c for many people with diabetes, at substantially reduced treatment costs,” Dr. Ludwig and colleagues wrote in the JCI review. “High-quality randomized controlled trials, with intensive support for behavior changes, will be needed to address this possibility and assess long-term safety and sustainability. With total medical costs of diabetes in the United States approaching $1 billion a day, this research must assume high priority.”
This clinical report was commissioned by the AAP. Dr. Ludwig received royalties for books that recommend a carbohydrate-modified diet.
This article was updated 9/20/23.
according to a new clinical report.
Citing a lack of high-quality data and potential for adverse effects with carbohydrate restriction among younger individuals, lead author Anna Neyman, MD, of Indiana University, Indianapolis, and colleagues suggested that pediatric patients with type 2 diabetes should focus on reducing nutrient-poor carbohydrate intake, while those with type 1 diabetes should only pursue broader carbohydrate restriction under close medical supervision.
“There are no guidelines for restricting dietary carbohydrate consumption to reduce risk for diabetes or improve diabetes outcomes in youth,” the investigators wrote in Pediatrics. “Thus, there is a need to provide practical recommendations for pediatricians regarding the use of low-carbohydrate diets in patients who elect to follow these diets, including those with type 1 diabetes and for patients with obesity, prediabetes, and type 2 diabetes.”
Their new report includes a summary of the various types of carbohydrate-restricted diets, a review of available evidence for these diets among pediatric patients with type 1 and type 2 diabetes, and several practical recommendations based on their findings.
Dr. Neyman and colleagues first noted a lack of standardization in describing the various tiers of carbohydrate restriction; however, they offered some rough guidelines. Compared with a typical, balanced diet, which includes 45%-65% of calories from carbohydrates, a moderately restrictive diet includes 26%-44% of calories from carbohydrates, while a low-carb diet includes less than 26% of calories from carbs. Further down the scale, very low-carb diets and ketogenic diets call for 20-50 g of carbs per day or less than 20 g of carbs per day, respectively.
“There is evidence from adult studies that these diets can be associated with significant weight loss, reduction in insulin levels or insulin requirements, and improvement in glucose control,” the investigators noted. “Nevertheless, there is a lack of long-term safety and efficacy outcomes in youth.”
They went on to cite a range of safety concerns, including “growth deceleration, nutritional deficiencies, poor bone health, nutritional ketosis that cannot be distinguished from ketosis resulting from insulin deficiency, and disordered eating behaviors.”
“Body dissatisfaction associated with restrictive dieting practices places children and adolescents at risk for inadequate dietary intake, excessive weight gain resulting from binge-eating after restricting food intake, and use of harmful weight-control strategies,” the investigators wrote. “Moreover, restrictive dieting practices may negatively impact mental health and self-concept and are directly associated with decreased mood and increased feelings of anxiety.”
Until more evidence is available, Dr. Neyman and colleagues advised adherence to a balanced diet, including increased dietary fiber and reduced consumption of ultra-processed carbohydrates.
“Eliminating sugary beverages and juices significantly improves blood glucose and weight management in children and adolescents,” they noted.
For pediatric patients with type 1 diabetes, the investigators suggested that low-carb and very low-carb diets should only be pursued “under close diabetes care team supervision utilizing safety guidelines.”
Lack of evidence is the problem
David Ludwig, MD, PhD, codirector of the New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, and professor of pediatrics at Harvard Medical School, also in Boston, said the review is “rather general” and “reiterates common, although not always fair, concerns about carbohydrate restriction.”
“The main issue they highlight is the lack of evidence, especially from clinical trials, for a low-carbohydrate diet in children, as related to diabetes,” Dr. Ludwig said in a written comment, noting that this is indeed an issue. “However, what needs to be recognized is that a conventional high-carbohydrate diet has never been shown to be superior in adults or children for diabetes. Furthermore, whereas a poorly formulated low-carb diet may have adverse effects and risks (e.g., nutrient deficiencies), so can a high-carbohydrate diet – including an increase in triglycerides and other risk factors comprising metabolic syndrome.”
He said that the “main challenge in diabetes is to control blood glucose after eating,” and a high-carb makes this more difficult, as it requires more insulin after a meal than a low-carb meal would require, and increases risk of subsequent hypoglycemia.
For those interested in an alternative perspective to the AAP clinical report, Dr. Ludwig recommended two of his recent review articles, including one published in the Journal of Nutrition and another from the Journal of Clinical Investigation. In both, notes the long history of carbohydrate restriction for patients with diabetes, with usage dating back to the 1700s. Although the diet fell out of favor with the introduction of insulin, Dr. Ludwig believes that it needs to be reconsidered, and is more than a passing fad.
“Preliminary research suggests that this dietary approach might transform clinical management and perhaps normalize HbA1c for many people with diabetes, at substantially reduced treatment costs,” Dr. Ludwig and colleagues wrote in the JCI review. “High-quality randomized controlled trials, with intensive support for behavior changes, will be needed to address this possibility and assess long-term safety and sustainability. With total medical costs of diabetes in the United States approaching $1 billion a day, this research must assume high priority.”
This clinical report was commissioned by the AAP. Dr. Ludwig received royalties for books that recommend a carbohydrate-modified diet.
This article was updated 9/20/23.
FROM PEDIATRICS
Smartphones for children with type 1 diabetes: Cause for concern?
My young patient with type 1 diabetes (T1D) had her cell phone out to provide a share code for her Dexcom clarity app as she was checking into her visit. As my nurse was recording the code, the patient asked him, “Hey, can you add me on Snapchat?”
Her father scrolled through his own Facebook feed in the chair next to her, showing no concern that his daughter was looking to connect with an adult on a social media platform. Meanwhile, we were all grateful that the little girl, who had had a seizure due to hypoglycemia in her preschool and pre–continuous glucose monitoring (CGM) years, had access to the tools harnessed within the sparkly encased phone she held in her small hands. But did anyone in the room fully understand the potential dangers?
We are living in an exhilarating era of diabetes technology, a treatment environment that I couldn’t have dreamed of during my pediatric endocrinology fellowship. T1D is a volatile condition that changes day to day, especially in growing children. A short decade ago, the best CGM available was a bulky device on loan to patients for 3 days at a time. Information was later downloaded in-office to get a better idea of general glucose trends, if insurance would approve its use at all.
Now, we have a variety of very wearable and accurate disposable CGMs accessible to most patients. Every major insulin pump has available closed-loop capabilities. Some patients can dose from apps on their cell phones rather than juggle another device or draw attention to an insulin pump at the cafeteria table.
These developments have been game changers for children and teenagers with diabetes and for their families. When wondering whether an athlete’s dazed appearance on a soccer field was due to hypoglycemia, a parent no longer must demand that a coach pull the player – a quick glance at a smartphone app can verify the blood glucose and change rate. Children can use programs and search engines to quickly verify carbohydrate counts. Life360 and other tracking programs have increased parental feelings of security, especially with young drivers living with a chronic medical condition.
The inevitable outcome of this available technology is that children living with T1D are given cell phones far earlier than are their siblings or peers owing to “necessity.” Parents understandably want a means to stay in close contact with their children in case of a medical emergency. As a physician and mother of young children, I am thankful for the technology that keeps my patients safer and that allows them to fully participate in everything from sports to travel to an uninterrupted night’s sleep.
Smartphone presence in classrooms empowers teachers, students, parents, and school nurses to be aware of glycemic trends and prevent hypoglycemic emergencies. Smartphones have also shown to be a major distraction in that setting, causing many schools to ban their use entirely. Video apps such as YouTube and TikTok can provide a wealth of support and medical information but may also open the door to misinformation and dangerous social contagion, particularly surrounding disordered eating. Informative podcasts such as The Juicebox Podcast and online forums provide incredible support for families, but the constant siren call of a phone in their pockets leads to distracted parents constantly tending to other conversations or responding to ever more demanding employers rather than focusing on face-to-face education sessions.
The Surgeon General recently released a report concerning social media use in children. This eye-opening report revealed that one-third of children admitted to using their cell phones “almost constantly.” Social media use is associated with higher rates of anxiety and depression, especially in teen girls. This is particularly concerning for children with T1D, who are more likely to suffer from these conditions.
Beyond mental health concerns, especially to developing brains, unfettered Internet use increases the risk that children are exposed to predators and harmful content. The online safety monitoring platform Bark shared data from its 2021 surveillance. Bark found that 72% of tweens and 85% of teens were involved in an online bullying situation. Sixty-nine percent of tweens and 91% of teens encountered nudity or sexual content. Ten percent of tweens and 21% of teens encountered predatory behavior.
These alarming finds mirror the prevalence suggested by conversations in my office. I hear reports of my patients sneaking out at night to meet adults they met through social media, having suicidal ideation and attempts after Internet bullying, and sharing earnest belief in bizarre conspiracy theories gleaned from online forums that lead to dangerous health care practices.
Furthermore, time is a finite resource. Teens who are spending an average of 3.5 hours daily on their devices are running out of time to play, study, and grow extracurricular interests. My friend who coaches high school baseball lamented recently the poor athleticism in his recent teams. He theorized that his players had spent their summers on tablets rather than playing catch or climbing trees. The resulting declines in exercise in young people only serve to worsen the childhood obesity epidemic.
What is a concerned parent to do? First, all phones have controls that allow parents to choose which apps are allowed and which are blocked. Caregivers must understand how various social media platforms work. Installing programs such as Bark provides an additional layer of monitoring, though these are no substitute for parental vigilance. Importantly, parents should talk to their children about their concerns regarding social media.
Sadly, I have often noticed that caregivers pity the extra hardships their children endure as the result of T1D and other chronic diseases. Being lax with rules to attempt to compensate for other suffering is far too tempting. The goal is for children and teens living with T1D to have a full and normal childhood, and unrestricted smartphone access and early social media use should not be the goal for any child. For every family, a media use plan is a smart approach. The American Academy of Pediatrics suggests several commonsense steps to use technology wisely, and parents often must address their own relationships with their devices to model healthy engagement.
As health care professionals, we owe it to our patients to discuss the ups and downs of technology with our patients. We can’t ostrich our way through this. We can point our patients and families to supportive groups such as Osprey (Old School Parents Raising Engaged Youth), founded by Ben and Erin Napier from the HGTV show Home Town along with my college friends Taylor and Dr. Catherine Sledge. Wait Until 8th provides information and motivation for parents to make wise choices regarding phone use for their children. The documentary Childhood 2.0 is another compelling resource developed by pediatric emergency physician Dr. Free Hess and her team that summarizes many of these concerns.
In another decade, many of these dangers will be far clearer. As ubiquitous as smartphone misuse is in our society, I remain hopeful that our society will change its behaviors. Just because “everyone else” allows an unhealthy relationship with technology doesn’t mean that we should for our children.
When I was a child, smoking was glamorized in movies and restaurants had dedicated smoking sections. After strong public policy efforts, many geared toward children, smoking is now almost unthinkable. My 8-year-old asked me lately whether a lady smoking a cigarette in the car next to us would have to go to jail. I chose a career in pediatrics because I am an optimist at my very core. We can’t ignore the dangers associated with the wide door opened by mobile devices. We can celebrate the benefits while clearly facing the pitfalls.
Dr. Lilley is director of the pediatric diabetes and lipid program at the Mississippi Center for Advanced Medicine, Madison. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My young patient with type 1 diabetes (T1D) had her cell phone out to provide a share code for her Dexcom clarity app as she was checking into her visit. As my nurse was recording the code, the patient asked him, “Hey, can you add me on Snapchat?”
Her father scrolled through his own Facebook feed in the chair next to her, showing no concern that his daughter was looking to connect with an adult on a social media platform. Meanwhile, we were all grateful that the little girl, who had had a seizure due to hypoglycemia in her preschool and pre–continuous glucose monitoring (CGM) years, had access to the tools harnessed within the sparkly encased phone she held in her small hands. But did anyone in the room fully understand the potential dangers?
We are living in an exhilarating era of diabetes technology, a treatment environment that I couldn’t have dreamed of during my pediatric endocrinology fellowship. T1D is a volatile condition that changes day to day, especially in growing children. A short decade ago, the best CGM available was a bulky device on loan to patients for 3 days at a time. Information was later downloaded in-office to get a better idea of general glucose trends, if insurance would approve its use at all.
Now, we have a variety of very wearable and accurate disposable CGMs accessible to most patients. Every major insulin pump has available closed-loop capabilities. Some patients can dose from apps on their cell phones rather than juggle another device or draw attention to an insulin pump at the cafeteria table.
These developments have been game changers for children and teenagers with diabetes and for their families. When wondering whether an athlete’s dazed appearance on a soccer field was due to hypoglycemia, a parent no longer must demand that a coach pull the player – a quick glance at a smartphone app can verify the blood glucose and change rate. Children can use programs and search engines to quickly verify carbohydrate counts. Life360 and other tracking programs have increased parental feelings of security, especially with young drivers living with a chronic medical condition.
The inevitable outcome of this available technology is that children living with T1D are given cell phones far earlier than are their siblings or peers owing to “necessity.” Parents understandably want a means to stay in close contact with their children in case of a medical emergency. As a physician and mother of young children, I am thankful for the technology that keeps my patients safer and that allows them to fully participate in everything from sports to travel to an uninterrupted night’s sleep.
Smartphone presence in classrooms empowers teachers, students, parents, and school nurses to be aware of glycemic trends and prevent hypoglycemic emergencies. Smartphones have also shown to be a major distraction in that setting, causing many schools to ban their use entirely. Video apps such as YouTube and TikTok can provide a wealth of support and medical information but may also open the door to misinformation and dangerous social contagion, particularly surrounding disordered eating. Informative podcasts such as The Juicebox Podcast and online forums provide incredible support for families, but the constant siren call of a phone in their pockets leads to distracted parents constantly tending to other conversations or responding to ever more demanding employers rather than focusing on face-to-face education sessions.
The Surgeon General recently released a report concerning social media use in children. This eye-opening report revealed that one-third of children admitted to using their cell phones “almost constantly.” Social media use is associated with higher rates of anxiety and depression, especially in teen girls. This is particularly concerning for children with T1D, who are more likely to suffer from these conditions.
Beyond mental health concerns, especially to developing brains, unfettered Internet use increases the risk that children are exposed to predators and harmful content. The online safety monitoring platform Bark shared data from its 2021 surveillance. Bark found that 72% of tweens and 85% of teens were involved in an online bullying situation. Sixty-nine percent of tweens and 91% of teens encountered nudity or sexual content. Ten percent of tweens and 21% of teens encountered predatory behavior.
These alarming finds mirror the prevalence suggested by conversations in my office. I hear reports of my patients sneaking out at night to meet adults they met through social media, having suicidal ideation and attempts after Internet bullying, and sharing earnest belief in bizarre conspiracy theories gleaned from online forums that lead to dangerous health care practices.
Furthermore, time is a finite resource. Teens who are spending an average of 3.5 hours daily on their devices are running out of time to play, study, and grow extracurricular interests. My friend who coaches high school baseball lamented recently the poor athleticism in his recent teams. He theorized that his players had spent their summers on tablets rather than playing catch or climbing trees. The resulting declines in exercise in young people only serve to worsen the childhood obesity epidemic.
What is a concerned parent to do? First, all phones have controls that allow parents to choose which apps are allowed and which are blocked. Caregivers must understand how various social media platforms work. Installing programs such as Bark provides an additional layer of monitoring, though these are no substitute for parental vigilance. Importantly, parents should talk to their children about their concerns regarding social media.
Sadly, I have often noticed that caregivers pity the extra hardships their children endure as the result of T1D and other chronic diseases. Being lax with rules to attempt to compensate for other suffering is far too tempting. The goal is for children and teens living with T1D to have a full and normal childhood, and unrestricted smartphone access and early social media use should not be the goal for any child. For every family, a media use plan is a smart approach. The American Academy of Pediatrics suggests several commonsense steps to use technology wisely, and parents often must address their own relationships with their devices to model healthy engagement.
As health care professionals, we owe it to our patients to discuss the ups and downs of technology with our patients. We can’t ostrich our way through this. We can point our patients and families to supportive groups such as Osprey (Old School Parents Raising Engaged Youth), founded by Ben and Erin Napier from the HGTV show Home Town along with my college friends Taylor and Dr. Catherine Sledge. Wait Until 8th provides information and motivation for parents to make wise choices regarding phone use for their children. The documentary Childhood 2.0 is another compelling resource developed by pediatric emergency physician Dr. Free Hess and her team that summarizes many of these concerns.
In another decade, many of these dangers will be far clearer. As ubiquitous as smartphone misuse is in our society, I remain hopeful that our society will change its behaviors. Just because “everyone else” allows an unhealthy relationship with technology doesn’t mean that we should for our children.
When I was a child, smoking was glamorized in movies and restaurants had dedicated smoking sections. After strong public policy efforts, many geared toward children, smoking is now almost unthinkable. My 8-year-old asked me lately whether a lady smoking a cigarette in the car next to us would have to go to jail. I chose a career in pediatrics because I am an optimist at my very core. We can’t ignore the dangers associated with the wide door opened by mobile devices. We can celebrate the benefits while clearly facing the pitfalls.
Dr. Lilley is director of the pediatric diabetes and lipid program at the Mississippi Center for Advanced Medicine, Madison. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My young patient with type 1 diabetes (T1D) had her cell phone out to provide a share code for her Dexcom clarity app as she was checking into her visit. As my nurse was recording the code, the patient asked him, “Hey, can you add me on Snapchat?”
Her father scrolled through his own Facebook feed in the chair next to her, showing no concern that his daughter was looking to connect with an adult on a social media platform. Meanwhile, we were all grateful that the little girl, who had had a seizure due to hypoglycemia in her preschool and pre–continuous glucose monitoring (CGM) years, had access to the tools harnessed within the sparkly encased phone she held in her small hands. But did anyone in the room fully understand the potential dangers?
We are living in an exhilarating era of diabetes technology, a treatment environment that I couldn’t have dreamed of during my pediatric endocrinology fellowship. T1D is a volatile condition that changes day to day, especially in growing children. A short decade ago, the best CGM available was a bulky device on loan to patients for 3 days at a time. Information was later downloaded in-office to get a better idea of general glucose trends, if insurance would approve its use at all.
Now, we have a variety of very wearable and accurate disposable CGMs accessible to most patients. Every major insulin pump has available closed-loop capabilities. Some patients can dose from apps on their cell phones rather than juggle another device or draw attention to an insulin pump at the cafeteria table.
These developments have been game changers for children and teenagers with diabetes and for their families. When wondering whether an athlete’s dazed appearance on a soccer field was due to hypoglycemia, a parent no longer must demand that a coach pull the player – a quick glance at a smartphone app can verify the blood glucose and change rate. Children can use programs and search engines to quickly verify carbohydrate counts. Life360 and other tracking programs have increased parental feelings of security, especially with young drivers living with a chronic medical condition.
The inevitable outcome of this available technology is that children living with T1D are given cell phones far earlier than are their siblings or peers owing to “necessity.” Parents understandably want a means to stay in close contact with their children in case of a medical emergency. As a physician and mother of young children, I am thankful for the technology that keeps my patients safer and that allows them to fully participate in everything from sports to travel to an uninterrupted night’s sleep.
Smartphone presence in classrooms empowers teachers, students, parents, and school nurses to be aware of glycemic trends and prevent hypoglycemic emergencies. Smartphones have also shown to be a major distraction in that setting, causing many schools to ban their use entirely. Video apps such as YouTube and TikTok can provide a wealth of support and medical information but may also open the door to misinformation and dangerous social contagion, particularly surrounding disordered eating. Informative podcasts such as The Juicebox Podcast and online forums provide incredible support for families, but the constant siren call of a phone in their pockets leads to distracted parents constantly tending to other conversations or responding to ever more demanding employers rather than focusing on face-to-face education sessions.
The Surgeon General recently released a report concerning social media use in children. This eye-opening report revealed that one-third of children admitted to using their cell phones “almost constantly.” Social media use is associated with higher rates of anxiety and depression, especially in teen girls. This is particularly concerning for children with T1D, who are more likely to suffer from these conditions.
Beyond mental health concerns, especially to developing brains, unfettered Internet use increases the risk that children are exposed to predators and harmful content. The online safety monitoring platform Bark shared data from its 2021 surveillance. Bark found that 72% of tweens and 85% of teens were involved in an online bullying situation. Sixty-nine percent of tweens and 91% of teens encountered nudity or sexual content. Ten percent of tweens and 21% of teens encountered predatory behavior.
These alarming finds mirror the prevalence suggested by conversations in my office. I hear reports of my patients sneaking out at night to meet adults they met through social media, having suicidal ideation and attempts after Internet bullying, and sharing earnest belief in bizarre conspiracy theories gleaned from online forums that lead to dangerous health care practices.
Furthermore, time is a finite resource. Teens who are spending an average of 3.5 hours daily on their devices are running out of time to play, study, and grow extracurricular interests. My friend who coaches high school baseball lamented recently the poor athleticism in his recent teams. He theorized that his players had spent their summers on tablets rather than playing catch or climbing trees. The resulting declines in exercise in young people only serve to worsen the childhood obesity epidemic.
What is a concerned parent to do? First, all phones have controls that allow parents to choose which apps are allowed and which are blocked. Caregivers must understand how various social media platforms work. Installing programs such as Bark provides an additional layer of monitoring, though these are no substitute for parental vigilance. Importantly, parents should talk to their children about their concerns regarding social media.
Sadly, I have often noticed that caregivers pity the extra hardships their children endure as the result of T1D and other chronic diseases. Being lax with rules to attempt to compensate for other suffering is far too tempting. The goal is for children and teens living with T1D to have a full and normal childhood, and unrestricted smartphone access and early social media use should not be the goal for any child. For every family, a media use plan is a smart approach. The American Academy of Pediatrics suggests several commonsense steps to use technology wisely, and parents often must address their own relationships with their devices to model healthy engagement.
As health care professionals, we owe it to our patients to discuss the ups and downs of technology with our patients. We can’t ostrich our way through this. We can point our patients and families to supportive groups such as Osprey (Old School Parents Raising Engaged Youth), founded by Ben and Erin Napier from the HGTV show Home Town along with my college friends Taylor and Dr. Catherine Sledge. Wait Until 8th provides information and motivation for parents to make wise choices regarding phone use for their children. The documentary Childhood 2.0 is another compelling resource developed by pediatric emergency physician Dr. Free Hess and her team that summarizes many of these concerns.
In another decade, many of these dangers will be far clearer. As ubiquitous as smartphone misuse is in our society, I remain hopeful that our society will change its behaviors. Just because “everyone else” allows an unhealthy relationship with technology doesn’t mean that we should for our children.
When I was a child, smoking was glamorized in movies and restaurants had dedicated smoking sections. After strong public policy efforts, many geared toward children, smoking is now almost unthinkable. My 8-year-old asked me lately whether a lady smoking a cigarette in the car next to us would have to go to jail. I chose a career in pediatrics because I am an optimist at my very core. We can’t ignore the dangers associated with the wide door opened by mobile devices. We can celebrate the benefits while clearly facing the pitfalls.
Dr. Lilley is director of the pediatric diabetes and lipid program at the Mississippi Center for Advanced Medicine, Madison. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.