Diabetes

Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.

Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
 

Precision Focus

Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.

“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”

Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”

As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
 

Spanish ‘Prescription Guide’

During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.

Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”

He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”

The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”

Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”

Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”

“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
 

Active Breaks

Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.

According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.

César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.

“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.

The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.

“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.

Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
 

Exerkines and Poly Pills

Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.

Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.

“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”

Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.

He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”

“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.

Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.

Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
 

Precision Focus

Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.

“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”

Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”

As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
 

Spanish ‘Prescription Guide’

During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.

Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”

He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”

The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”

Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”

Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”

“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
 

Active Breaks

Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.

According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.

César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.

“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.

The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.

“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.

Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
 

Exerkines and Poly Pills

Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.

Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.

“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”

Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.

He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”

“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.

Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.

Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
 

Precision Focus

Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.

“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”

Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”

As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
 

Spanish ‘Prescription Guide’

During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.

Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”

He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”

The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”

Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”

Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”

“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
 

Active Breaks

Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.

According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.

César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.

“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.

The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.

“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.

Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
 

Exerkines and Poly Pills

Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.

Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.

“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”

Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.

He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”

“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.

Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.

WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.

Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.

Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”

Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.

A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.

Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.

“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”

The Knowns And Unknowns of CGM in Pregnancy

The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.

The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.

Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.

Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)

More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”

There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”

And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).

Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.

Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).

The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.

CGM in Type 2, GDM

CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”

While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.

Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
 

Is Preventing Maternal Hypoglycemia Possible?

Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.

The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.

Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.

In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.

Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).

The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”

Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.

Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.

Rethinking Intrapartum Care

Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.

A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).

Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).

Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).

Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).

The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.

Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.

The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.

Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.

“I do think we need to rethink our current recommendations,” she said.

Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A diagnosis of type 2 diabetes (T2D) at a younger age is associated with an increased cancer risk, while the risk drops for T2D diagnosed at age 75 and older.

METHODOLOGY:

• A T2D diagnosis at a younger age is associated with a greater risk for complications and comorbidities, such as cardiovascular and kidney diseases, retinopathy, and dementia than that occurring at an older age.
• The study evaluated the association between the age at T2D diagnosis and subsequent risk for overall and 14 site-specific cancers in a Shanghai, China, cohort of 428,568 patients newly diagnosed with T2D (about half women) from 2011 to 2018.
• New cases of cancer from the T2D diagnosis to 2018 were identified through a tumor registry.
• Patients were categorized into six groups based on their age at T2D diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥ 75 years.
• The incidence rates of overall and 14 site-specific cancers were compared between patients with T2D and the general Shanghai population (older than 20 years).

TAKEAWAY:

• Compared to the general population, T2D increased the relative risk for all-cause cancer by 10% (standardized incidence ratios [SIRs], 1.10; 95% CI, 1.09-1.12).
• Compared with the general population, the overall cancer incidence risk (SIR) was higher among those diagnosed with T2D at a younger age:
• 20-54 years: 1.48 (95% CI, 1.41-1.54)
• 55-59 years: 1.30 (95% CI, 1.25-1.35)
• 60-64 years: 1.19 (95% CI, 1.15-1.23)
• 65-69 years: 1.16 (95% CI, 1.12-1.20)
• 70-74 years: 1.06 (95% CI, 1.02-1.10)
• The overall cancer incidence risk in patients diagnosed with T2D at age ≥ 75 years was even lower than that in the general population (SIR, 0.86; 95% CI, 0.84-0.89).
• The risk (SIR) for most site-specific cancers (including respiratory, colorectal, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancers and lymphoma) decreased with increasing age at T2D diagnosis.

IN PRACTICE:

“Our findings suggest that the carcinogenicity of T2D differs markedly by age at diagnosis and highlights the necessity of stratifying patients according to diagnosis age in management, screening, and preventative strategies,” wrote the authors.

SOURCE:

The study, led by Yanyun Li, Division of Chronic Non-Communicable Disease and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

Data on smoking history, alcohol consumption, and physical activity were available for nearly 60% of patients with T2D. The findings might only apply to patients with T2D who survive longer than the average and are therefore less applicable to the general population with diabetes. Patients with young-onset T2D had not reached the age where cancers are more prevalent despite as many as 8 years of follow-up.

DISCLOSURES:

This work was supported by the Foundation of National Facility for Translational Medicine, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Three-Year Action Plan of Shanghai Public Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diagnosis of type 2 diabetes (T2D) at a younger age is associated with an increased cancer risk, while the risk drops for T2D diagnosed at age 75 and older.

METHODOLOGY:

• A T2D diagnosis at a younger age is associated with a greater risk for complications and comorbidities, such as cardiovascular and kidney diseases, retinopathy, and dementia than that occurring at an older age.
• The study evaluated the association between the age at T2D diagnosis and subsequent risk for overall and 14 site-specific cancers in a Shanghai, China, cohort of 428,568 patients newly diagnosed with T2D (about half women) from 2011 to 2018.
• New cases of cancer from the T2D diagnosis to 2018 were identified through a tumor registry.
• Patients were categorized into six groups based on their age at T2D diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥ 75 years.
• The incidence rates of overall and 14 site-specific cancers were compared between patients with T2D and the general Shanghai population (older than 20 years).

TAKEAWAY:

• Compared to the general population, T2D increased the relative risk for all-cause cancer by 10% (standardized incidence ratios [SIRs], 1.10; 95% CI, 1.09-1.12).
• Compared with the general population, the overall cancer incidence risk (SIR) was higher among those diagnosed with T2D at a younger age:
• 20-54 years: 1.48 (95% CI, 1.41-1.54)
• 55-59 years: 1.30 (95% CI, 1.25-1.35)
• 60-64 years: 1.19 (95% CI, 1.15-1.23)
• 65-69 years: 1.16 (95% CI, 1.12-1.20)
• 70-74 years: 1.06 (95% CI, 1.02-1.10)
• The overall cancer incidence risk in patients diagnosed with T2D at age ≥ 75 years was even lower than that in the general population (SIR, 0.86; 95% CI, 0.84-0.89).
• The risk (SIR) for most site-specific cancers (including respiratory, colorectal, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancers and lymphoma) decreased with increasing age at T2D diagnosis.

IN PRACTICE:

“Our findings suggest that the carcinogenicity of T2D differs markedly by age at diagnosis and highlights the necessity of stratifying patients according to diagnosis age in management, screening, and preventative strategies,” wrote the authors.

SOURCE:

The study, led by Yanyun Li, Division of Chronic Non-Communicable Disease and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

Data on smoking history, alcohol consumption, and physical activity were available for nearly 60% of patients with T2D. The findings might only apply to patients with T2D who survive longer than the average and are therefore less applicable to the general population with diabetes. Patients with young-onset T2D had not reached the age where cancers are more prevalent despite as many as 8 years of follow-up.

DISCLOSURES:

This work was supported by the Foundation of National Facility for Translational Medicine, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Three-Year Action Plan of Shanghai Public Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diagnosis of type 2 diabetes (T2D) at a younger age is associated with an increased cancer risk, while the risk drops for T2D diagnosed at age 75 and older.

METHODOLOGY:

• A T2D diagnosis at a younger age is associated with a greater risk for complications and comorbidities, such as cardiovascular and kidney diseases, retinopathy, and dementia than that occurring at an older age.
• The study evaluated the association between the age at T2D diagnosis and subsequent risk for overall and 14 site-specific cancers in a Shanghai, China, cohort of 428,568 patients newly diagnosed with T2D (about half women) from 2011 to 2018.
• New cases of cancer from the T2D diagnosis to 2018 were identified through a tumor registry.
• Patients were categorized into six groups based on their age at T2D diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥ 75 years.
• The incidence rates of overall and 14 site-specific cancers were compared between patients with T2D and the general Shanghai population (older than 20 years).

TAKEAWAY:

• Compared to the general population, T2D increased the relative risk for all-cause cancer by 10% (standardized incidence ratios [SIRs], 1.10; 95% CI, 1.09-1.12).
• Compared with the general population, the overall cancer incidence risk (SIR) was higher among those diagnosed with T2D at a younger age:
• 20-54 years: 1.48 (95% CI, 1.41-1.54)
• 55-59 years: 1.30 (95% CI, 1.25-1.35)
• 60-64 years: 1.19 (95% CI, 1.15-1.23)
• 65-69 years: 1.16 (95% CI, 1.12-1.20)
• 70-74 years: 1.06 (95% CI, 1.02-1.10)
• The overall cancer incidence risk in patients diagnosed with T2D at age ≥ 75 years was even lower than that in the general population (SIR, 0.86; 95% CI, 0.84-0.89).
• The risk (SIR) for most site-specific cancers (including respiratory, colorectal, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancers and lymphoma) decreased with increasing age at T2D diagnosis.

IN PRACTICE:

“Our findings suggest that the carcinogenicity of T2D differs markedly by age at diagnosis and highlights the necessity of stratifying patients according to diagnosis age in management, screening, and preventative strategies,” wrote the authors.

SOURCE:

The study, led by Yanyun Li, Division of Chronic Non-Communicable Disease and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

Data on smoking history, alcohol consumption, and physical activity were available for nearly 60% of patients with T2D. The findings might only apply to patients with T2D who survive longer than the average and are therefore less applicable to the general population with diabetes. Patients with young-onset T2D had not reached the age where cancers are more prevalent despite as many as 8 years of follow-up.

DISCLOSURES:

This work was supported by the Foundation of National Facility for Translational Medicine, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Three-Year Action Plan of Shanghai Public Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher high-density lipoprotein cholesterol (HDL-C) levels show a positive association with prediabetes reversal to normoglycemia in Chinese adults, but only up to a certain threshold.

METHODOLOGY:

• Researchers examined the correlation between HDL-C levels and the reversion of people with prediabetes to normoglycemia in a secondary analysis of data from a population-based cohort study.
• The analysis included 15,420 Chinese patients with prediabetes who underwent health screening between 2010 and 2016 (mean age, 51 ± 13 years; 5414 (35%) women).
• The outcome measure, reversion to normoglycemia, was determined by no self-reported diabetic event and fasting plasma glucose < 5.6 mmol/L at follow-up.
• They categorized the adults into four groups on the basis of HDL-C quartiles.
• They used multiple statistical models to investigate the association between HDL-C levels and reversion from prediabetes, assess the linearity of the association, and account for independent variables and confounding factors.

TAKEAWAY:

• After a median follow-up of nearly 3 years, 6627 (43%) of patients with prediabetes had a reversion to normoglycemia.
• The groups with higher HDL-C levels had a higher likelihood of prediabetes reversal to normoglycemia (adjusted hazard ratio [HR], 1.90; P < .001).
• They found a nonlinear association and threshold effect: The probability of reversal from prediabetes to normoglycemia stabilized rather than continued to increase at an inflection point (1.54 mmol/L in men, 1.62 mmol/L in women).
• A significant positive correlation with reversal to normoglycemia was observed below the HDL-C threshold (men: HR, 2.78; 95% CI, 2.37-3.26; women: HR, 2.22; 95% CI, 1.80-2.73).

IN PRACTICE:

“Keeping HDL-C levels near the inflection point in patients with prediabetes may greatly increase the likelihood of reversion from prediabetes to normoglycemia,” the authors wrote.

SOURCE:

The study, with lead author Zihe Mo, Department of Physical Examination, Dongguan Tungwah Hospital, Dongguan, China, was published online in Scientific Reports.

LIMITATIONS:

The study included individuals of Chinese descent, necessitating more studies into the HDL-C and normoglycemia relationship across diverse genetic backgrounds. The study relied solely on fasting plasma glucose measurements and was unable to capture the entirety of prediabetes complexity. As a secondary analysis of previously published data, the study faces limitations in managing unmeasured variables not initially included in the dataset. The observational study cannot determine a causal relationship between HDL-C and reversion from prediabetes to normoglycemia.

DISCLOSURES:

The study was supported by the Natural Science Funding of China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher high-density lipoprotein cholesterol (HDL-C) levels show a positive association with prediabetes reversal to normoglycemia in Chinese adults, but only up to a certain threshold.

METHODOLOGY:

• Researchers examined the correlation between HDL-C levels and the reversion of people with prediabetes to normoglycemia in a secondary analysis of data from a population-based cohort study.
• The analysis included 15,420 Chinese patients with prediabetes who underwent health screening between 2010 and 2016 (mean age, 51 ± 13 years; 5414 (35%) women).
• The outcome measure, reversion to normoglycemia, was determined by no self-reported diabetic event and fasting plasma glucose < 5.6 mmol/L at follow-up.
• They categorized the adults into four groups on the basis of HDL-C quartiles.
• They used multiple statistical models to investigate the association between HDL-C levels and reversion from prediabetes, assess the linearity of the association, and account for independent variables and confounding factors.

TAKEAWAY:

• After a median follow-up of nearly 3 years, 6627 (43%) of patients with prediabetes had a reversion to normoglycemia.
• The groups with higher HDL-C levels had a higher likelihood of prediabetes reversal to normoglycemia (adjusted hazard ratio [HR], 1.90; P < .001).
• They found a nonlinear association and threshold effect: The probability of reversal from prediabetes to normoglycemia stabilized rather than continued to increase at an inflection point (1.54 mmol/L in men, 1.62 mmol/L in women).
• A significant positive correlation with reversal to normoglycemia was observed below the HDL-C threshold (men: HR, 2.78; 95% CI, 2.37-3.26; women: HR, 2.22; 95% CI, 1.80-2.73).

IN PRACTICE:

“Keeping HDL-C levels near the inflection point in patients with prediabetes may greatly increase the likelihood of reversion from prediabetes to normoglycemia,” the authors wrote.

SOURCE:

The study, with lead author Zihe Mo, Department of Physical Examination, Dongguan Tungwah Hospital, Dongguan, China, was published online in Scientific Reports.

LIMITATIONS:

The study included individuals of Chinese descent, necessitating more studies into the HDL-C and normoglycemia relationship across diverse genetic backgrounds. The study relied solely on fasting plasma glucose measurements and was unable to capture the entirety of prediabetes complexity. As a secondary analysis of previously published data, the study faces limitations in managing unmeasured variables not initially included in the dataset. The observational study cannot determine a causal relationship between HDL-C and reversion from prediabetes to normoglycemia.

DISCLOSURES:

The study was supported by the Natural Science Funding of China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher high-density lipoprotein cholesterol (HDL-C) levels show a positive association with prediabetes reversal to normoglycemia in Chinese adults, but only up to a certain threshold.

METHODOLOGY:

• Researchers examined the correlation between HDL-C levels and the reversion of people with prediabetes to normoglycemia in a secondary analysis of data from a population-based cohort study.
• The analysis included 15,420 Chinese patients with prediabetes who underwent health screening between 2010 and 2016 (mean age, 51 ± 13 years; 5414 (35%) women).
• The outcome measure, reversion to normoglycemia, was determined by no self-reported diabetic event and fasting plasma glucose < 5.6 mmol/L at follow-up.
• They categorized the adults into four groups on the basis of HDL-C quartiles.
• They used multiple statistical models to investigate the association between HDL-C levels and reversion from prediabetes, assess the linearity of the association, and account for independent variables and confounding factors.

TAKEAWAY:

• After a median follow-up of nearly 3 years, 6627 (43%) of patients with prediabetes had a reversion to normoglycemia.
• The groups with higher HDL-C levels had a higher likelihood of prediabetes reversal to normoglycemia (adjusted hazard ratio [HR], 1.90; P < .001).
• They found a nonlinear association and threshold effect: The probability of reversal from prediabetes to normoglycemia stabilized rather than continued to increase at an inflection point (1.54 mmol/L in men, 1.62 mmol/L in women).
• A significant positive correlation with reversal to normoglycemia was observed below the HDL-C threshold (men: HR, 2.78; 95% CI, 2.37-3.26; women: HR, 2.22; 95% CI, 1.80-2.73).

IN PRACTICE:

“Keeping HDL-C levels near the inflection point in patients with prediabetes may greatly increase the likelihood of reversion from prediabetes to normoglycemia,” the authors wrote.

SOURCE:

The study, with lead author Zihe Mo, Department of Physical Examination, Dongguan Tungwah Hospital, Dongguan, China, was published online in Scientific Reports.

LIMITATIONS:

The study included individuals of Chinese descent, necessitating more studies into the HDL-C and normoglycemia relationship across diverse genetic backgrounds. The study relied solely on fasting plasma glucose measurements and was unable to capture the entirety of prediabetes complexity. As a secondary analysis of previously published data, the study faces limitations in managing unmeasured variables not initially included in the dataset. The observational study cannot determine a causal relationship between HDL-C and reversion from prediabetes to normoglycemia.

DISCLOSURES:

The study was supported by the Natural Science Funding of China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

The blockbuster drugs of the century have arrived: glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These drugs were developed to control blood sugar but have gained immense popularity for weight loss. Patients are clamoring for the drugs, and physicians are inundated with patient inquiries.

As doctors in primary care and other specialties are discovering, the GLP-1 RA drugs add another layer of complexity to the long-term management of a chronic disease. Managing diabetes and obesity requires a multidisciplinary team and a multispecialty treatment approach.

That’s why it’s more important than ever to know when and why to refer patients to an endocrinologist, who can offer unparalleled expertise as part of a multidisciplinary treatment approach.

Here are 10 reasons to refer your patients with diabetes to an endocrinologist.

1. To help make an optimal medication choice. Endocrinologists navigate diabetes management by considering individualized glycemic, cardiorenal, and weight goals as per guidelines, incorporating knowledge of medication side effects, simplifying regimens for adherence, and addressing practical factors like access and cost. Optimal medication selection is crucial, as a recent study found that nearly two thirds of patients altered their treatment by discontinuing their medication, switching their medication, or changing the dose of their medication within 12 months. Whether diabetes is controlled or uncontrolled, patients should consult an endocrinologist due to the potential complexity of cases, including late autoimmune onset of diabetes; medication-induced diabetes; and factors such as age, fragility, and chronic illnesses.

2. To facilitate medication approvals, alternatives, and authorizations. Attaining medication approval for patients entails a nuanced understanding and resources. Through experience and careful consideration, endocrinologists develop insights into potential barriers, especially in cases where approval for specific medications necessitates prior failures with multiple GLP-1 RAs or antihyperglycemic agents. This expertise positions them to advocate effectively for alternative options, often involving the meticulous process of prior authorizations. Certain endocrinology practices may augment this endeavor by offering dedicated resources, such as a specialized prior authorization team.

3. To deal with diabetes complications. Endocrinologists can help address emerging issues in GLP-1 RA drugs such as retinopathy, gastroparesis, and mental health effects. They can also help manage coexisting conditions, such as addressing thyroid nodules before considering the use of GLP-1 RAs. Recognizing the interconnected nature of diabetes and its influence on diverse body systems, endocrinologists ensure a thorough and integrated management strategy for their patients.

4. To titrate other glucose-lowering agents. Patients with diabetes are often on combination therapy. Endocrinologists adeptly adjust and titrate these treatments to optimize glucose control while minimizing side effects like hypoglycemia. Beyond insulin, their expertise encompasses various glucose-lowering agents. Notably, patients who use GLP-1 RAs in combination with medications such as insulin secretagogues (eg, sulfonylurea) and insulin face an elevated risk for hypoglycemia, including severe cases, necessitating careful titration to mitigate these effects.

5. To integrate advances in diabetes technology. Endocrinologists stay abreast of technological advancements in diabetes care, incorporating innovations in monitoring and treatment strategies such as continuous glucose monitors and insulin pumps. This ensures that patients benefit from the latest technologies for more precise management of their condition.

6. To ensure a comprehensive care team. Endocrinologists engage in collaborative efforts with a multidisciplinary team composed of professionals like nurses, diabetes educators, and nutritionists. These experts may be situated within endocrinology offices or accessible through a well-established referral network. Together, the team delivers thorough counseling on medication use and effectively addresses essential lifestyle factors, ensuring a comprehensive approach to diabetes management.

7. To counsel on side effects and management. Ensuring adherence and persistence with medication therapy poses considerable challenges. One study noted discontinuation rates for non-insulin diabetes medications of about 38%, with a higher 50% rate for GLP-1 RA drugs. The study didn›t provide specific reasons for discontinuation, but discontinuation was lower when medications were prescribed by an endocrinologist. Endocrinologists can provide valuable guidance on potential medication side effects and their management. This proactive approach not only fosters patient understanding but also empowers individuals to promptly address side effects, significantly enhancing treatment adherence and overall effectiveness.

8. To work around drug shortages. Given their frequent involvement in prescribing and obtaining medications for patients, endocrinologists adeptly utilize community relationships to navigate medication shortages. Their awareness of drug availability provides patients with a strategic advantage in overcoming supply challenges.

9. To determine dosing equivalents. In situations where supply-chain shortages persist, a thorough understanding of alternative options and dosing equivalents becomes paramount for ensuring uninterrupted care.

To provide follow-up. Endocrinologists prioritize regular follow-ups, providing patients with dedicated time slots for 10. ongoing monitoring and adjustments to their treatment plans. This commitment to follow-up care contributes to sustained, optimal outcomes in diabetes management.

Navigating the intricate healthcare landscape requires a delicate balance between primary care proficiency and specialist expertise, with endocrinologists playing a pivotal role in diabetes management. Our collaborative strength lies in acknowledging challenges and resource limitations, especially a physician’s familiarity with the latest diabetes medications.

Dr. Jaisinghani has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from Novo Nordisk.

A version of this article appeared on Medscape.com.

The blockbuster drugs of the century have arrived: glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These drugs were developed to control blood sugar but have gained immense popularity for weight loss. Patients are clamoring for the drugs, and physicians are inundated with patient inquiries.

As doctors in primary care and other specialties are discovering, the GLP-1 RA drugs add another layer of complexity to the long-term management of a chronic disease. Managing diabetes and obesity requires a multidisciplinary team and a multispecialty treatment approach.

That’s why it’s more important than ever to know when and why to refer patients to an endocrinologist, who can offer unparalleled expertise as part of a multidisciplinary treatment approach.

Here are 10 reasons to refer your patients with diabetes to an endocrinologist.

1. To help make an optimal medication choice. Endocrinologists navigate diabetes management by considering individualized glycemic, cardiorenal, and weight goals as per guidelines, incorporating knowledge of medication side effects, simplifying regimens for adherence, and addressing practical factors like access and cost. Optimal medication selection is crucial, as a recent study found that nearly two thirds of patients altered their treatment by discontinuing their medication, switching their medication, or changing the dose of their medication within 12 months. Whether diabetes is controlled or uncontrolled, patients should consult an endocrinologist due to the potential complexity of cases, including late autoimmune onset of diabetes; medication-induced diabetes; and factors such as age, fragility, and chronic illnesses.

2. To facilitate medication approvals, alternatives, and authorizations. Attaining medication approval for patients entails a nuanced understanding and resources. Through experience and careful consideration, endocrinologists develop insights into potential barriers, especially in cases where approval for specific medications necessitates prior failures with multiple GLP-1 RAs or antihyperglycemic agents. This expertise positions them to advocate effectively for alternative options, often involving the meticulous process of prior authorizations. Certain endocrinology practices may augment this endeavor by offering dedicated resources, such as a specialized prior authorization team.

3. To deal with diabetes complications. Endocrinologists can help address emerging issues in GLP-1 RA drugs such as retinopathy, gastroparesis, and mental health effects. They can also help manage coexisting conditions, such as addressing thyroid nodules before considering the use of GLP-1 RAs. Recognizing the interconnected nature of diabetes and its influence on diverse body systems, endocrinologists ensure a thorough and integrated management strategy for their patients.

4. To titrate other glucose-lowering agents. Patients with diabetes are often on combination therapy. Endocrinologists adeptly adjust and titrate these treatments to optimize glucose control while minimizing side effects like hypoglycemia. Beyond insulin, their expertise encompasses various glucose-lowering agents. Notably, patients who use GLP-1 RAs in combination with medications such as insulin secretagogues (eg, sulfonylurea) and insulin face an elevated risk for hypoglycemia, including severe cases, necessitating careful titration to mitigate these effects.

5. To integrate advances in diabetes technology. Endocrinologists stay abreast of technological advancements in diabetes care, incorporating innovations in monitoring and treatment strategies such as continuous glucose monitors and insulin pumps. This ensures that patients benefit from the latest technologies for more precise management of their condition.

6. To ensure a comprehensive care team. Endocrinologists engage in collaborative efforts with a multidisciplinary team composed of professionals like nurses, diabetes educators, and nutritionists. These experts may be situated within endocrinology offices or accessible through a well-established referral network. Together, the team delivers thorough counseling on medication use and effectively addresses essential lifestyle factors, ensuring a comprehensive approach to diabetes management.

7. To counsel on side effects and management. Ensuring adherence and persistence with medication therapy poses considerable challenges. One study noted discontinuation rates for non-insulin diabetes medications of about 38%, with a higher 50% rate for GLP-1 RA drugs. The study didn›t provide specific reasons for discontinuation, but discontinuation was lower when medications were prescribed by an endocrinologist. Endocrinologists can provide valuable guidance on potential medication side effects and their management. This proactive approach not only fosters patient understanding but also empowers individuals to promptly address side effects, significantly enhancing treatment adherence and overall effectiveness.

8. To work around drug shortages. Given their frequent involvement in prescribing and obtaining medications for patients, endocrinologists adeptly utilize community relationships to navigate medication shortages. Their awareness of drug availability provides patients with a strategic advantage in overcoming supply challenges.

9. To determine dosing equivalents. In situations where supply-chain shortages persist, a thorough understanding of alternative options and dosing equivalents becomes paramount for ensuring uninterrupted care.

To provide follow-up. Endocrinologists prioritize regular follow-ups, providing patients with dedicated time slots for 10. ongoing monitoring and adjustments to their treatment plans. This commitment to follow-up care contributes to sustained, optimal outcomes in diabetes management.

Navigating the intricate healthcare landscape requires a delicate balance between primary care proficiency and specialist expertise, with endocrinologists playing a pivotal role in diabetes management. Our collaborative strength lies in acknowledging challenges and resource limitations, especially a physician’s familiarity with the latest diabetes medications.

Dr. Jaisinghani has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from Novo Nordisk.

A version of this article appeared on Medscape.com.

The blockbuster drugs of the century have arrived: glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These drugs were developed to control blood sugar but have gained immense popularity for weight loss. Patients are clamoring for the drugs, and physicians are inundated with patient inquiries.

As doctors in primary care and other specialties are discovering, the GLP-1 RA drugs add another layer of complexity to the long-term management of a chronic disease. Managing diabetes and obesity requires a multidisciplinary team and a multispecialty treatment approach.

That’s why it’s more important than ever to know when and why to refer patients to an endocrinologist, who can offer unparalleled expertise as part of a multidisciplinary treatment approach.

Here are 10 reasons to refer your patients with diabetes to an endocrinologist.

1. To help make an optimal medication choice. Endocrinologists navigate diabetes management by considering individualized glycemic, cardiorenal, and weight goals as per guidelines, incorporating knowledge of medication side effects, simplifying regimens for adherence, and addressing practical factors like access and cost. Optimal medication selection is crucial, as a recent study found that nearly two thirds of patients altered their treatment by discontinuing their medication, switching their medication, or changing the dose of their medication within 12 months. Whether diabetes is controlled or uncontrolled, patients should consult an endocrinologist due to the potential complexity of cases, including late autoimmune onset of diabetes; medication-induced diabetes; and factors such as age, fragility, and chronic illnesses.

2. To facilitate medication approvals, alternatives, and authorizations. Attaining medication approval for patients entails a nuanced understanding and resources. Through experience and careful consideration, endocrinologists develop insights into potential barriers, especially in cases where approval for specific medications necessitates prior failures with multiple GLP-1 RAs or antihyperglycemic agents. This expertise positions them to advocate effectively for alternative options, often involving the meticulous process of prior authorizations. Certain endocrinology practices may augment this endeavor by offering dedicated resources, such as a specialized prior authorization team.

3. To deal with diabetes complications. Endocrinologists can help address emerging issues in GLP-1 RA drugs such as retinopathy, gastroparesis, and mental health effects. They can also help manage coexisting conditions, such as addressing thyroid nodules before considering the use of GLP-1 RAs. Recognizing the interconnected nature of diabetes and its influence on diverse body systems, endocrinologists ensure a thorough and integrated management strategy for their patients.

4. To titrate other glucose-lowering agents. Patients with diabetes are often on combination therapy. Endocrinologists adeptly adjust and titrate these treatments to optimize glucose control while minimizing side effects like hypoglycemia. Beyond insulin, their expertise encompasses various glucose-lowering agents. Notably, patients who use GLP-1 RAs in combination with medications such as insulin secretagogues (eg, sulfonylurea) and insulin face an elevated risk for hypoglycemia, including severe cases, necessitating careful titration to mitigate these effects.

5. To integrate advances in diabetes technology. Endocrinologists stay abreast of technological advancements in diabetes care, incorporating innovations in monitoring and treatment strategies such as continuous glucose monitors and insulin pumps. This ensures that patients benefit from the latest technologies for more precise management of their condition.

6. To ensure a comprehensive care team. Endocrinologists engage in collaborative efforts with a multidisciplinary team composed of professionals like nurses, diabetes educators, and nutritionists. These experts may be situated within endocrinology offices or accessible through a well-established referral network. Together, the team delivers thorough counseling on medication use and effectively addresses essential lifestyle factors, ensuring a comprehensive approach to diabetes management.

7. To counsel on side effects and management. Ensuring adherence and persistence with medication therapy poses considerable challenges. One study noted discontinuation rates for non-insulin diabetes medications of about 38%, with a higher 50% rate for GLP-1 RA drugs. The study didn›t provide specific reasons for discontinuation, but discontinuation was lower when medications were prescribed by an endocrinologist. Endocrinologists can provide valuable guidance on potential medication side effects and their management. This proactive approach not only fosters patient understanding but also empowers individuals to promptly address side effects, significantly enhancing treatment adherence and overall effectiveness.

8. To work around drug shortages. Given their frequent involvement in prescribing and obtaining medications for patients, endocrinologists adeptly utilize community relationships to navigate medication shortages. Their awareness of drug availability provides patients with a strategic advantage in overcoming supply challenges.

9. To determine dosing equivalents. In situations where supply-chain shortages persist, a thorough understanding of alternative options and dosing equivalents becomes paramount for ensuring uninterrupted care.

To provide follow-up. Endocrinologists prioritize regular follow-ups, providing patients with dedicated time slots for 10. ongoing monitoring and adjustments to their treatment plans. This commitment to follow-up care contributes to sustained, optimal outcomes in diabetes management.

Navigating the intricate healthcare landscape requires a delicate balance between primary care proficiency and specialist expertise, with endocrinologists playing a pivotal role in diabetes management. Our collaborative strength lies in acknowledging challenges and resource limitations, especially a physician’s familiarity with the latest diabetes medications.

Dr. Jaisinghani has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from Novo Nordisk.

A version of this article appeared on Medscape.com.

The arrival of GLP-1 receptor agonists has revolutionized treatment options for people with obesity and medical practice.

This news organization recently hosted a panel of experts across specialties — including endocrinology, gastroenterology, and obesity medicine — to discuss these potentially life-changing medications and to answer questions from the audience.

Because of the flood of queries from our audience, we asked our panelists to address some of the questions that didn’t make the recording. Their answers are below.

Beverly Tchang, MD, endocrinologist, Weill Cornell Medicine, New York City

Audience member: Can you initiate glucagon-like peptide-1 agonists (GLP-1 RAs) as a primary drug in a patient with obesity and newly diagnosed type 2 diabetes?

BT: We often prescribe GLP-1 RAs to individuals with type 2 diabetes as a first-line medication. Guidelines from the American Diabetes Association are really emphasizing a patient-centered approach, and metformin may not be the best first-line medication anymore.

Audience member: What should clinicians know about dose titration of GLP-1 RAs in diabetic patients with renal disease, especially those in stages IV and V chronic kidney disease?

BT: GLP-1 RAs do not need to be renally dosed, but I still recommend conferring with the patient’s nephrologist because the glomerular filtration rate might decrease in the setting of dehydration. Because GLP1s suppress the thirst, not just appetite, patients can go all day without drinking water and not feel thirsty.

Michael Camilleri, MD, gastroenterologist, Mayo Clinic, Rochester, Minnesota

Audience member: Should GLP-1 RAs be held for 1 week or 4 weeks prior to surgery to reduce the patient’s risk for aspiration? And is tapering required?

MC: For a patient taking liraglutide, I would hold the drug for 1 week prior to surgery. For patients taking other GLP-1 RAs, including extended exenatide, I advise holding for between 2 and 3 weeks before the procedure. It’s also important to make sure the patient’s diabetes is well-controlled with other medications — not GLP-1 RAs — during this period.

After surgery, you can restart GLP-1 RA therapy once there is recovery of oral food intake and normal bowel function.

Audience member: Is treatment with GLP-1 RAs appropriate for a patient with a family history of colon cancer but an otherwise unremarkable medical and family history?

MC: I have not seen a contraindication to receiving GLP-1 RAs based on a family history of colorectal cancer or other malignancies. An analysis of the French national healthcare insurance system database has suggested 1-3 years use of GLP-1 RAs (exenatide, liraglutide, and dulaglutide) may be linked with increased occurrence of thyroid cancer. Data from 37 randomized controlled trials and 19 real-world studies having 16,839 patients in placebo control group, 16,550 patients in active control group, and 13,330 patients in real-world studies were analyzed in a 2023 systematic review and meta-analysis. Compared to placebo or active control treatments, occurrence of pancreatic cancer, thyroid cancer, and all neoplasms — benign, malignant, and otherwise unspecified — were similar in the semaglutide group.

Toshi Iroku-Malize, MD, MPH, MBA, FAAFP, family physician, Zucker School of Medicine, Hempstead, New York

Audience member: What do you do about elevated liver functions after starting treatment with GLP-1 RAs, and what do you do when a patient has reached their weight loss goal?

TI-M: I recommend monitoring the liver function tests, evaluating for underlying causes, such as viral hepatitis, alcohol-related damage, or problems with other medications, and consulting a gastroenterologist or liver specialist if necessary. It’s also important to discuss the risk-benefit of continuing on the GP-1 RA for that particular patient.

Audience member: What effects will GLP-1 RAs have on sleep-disordered breathing/obstructive sleep apnea (OSA)? Are you aware of any ongoing trials addressing this subject?

TI-M: GLP-1 RAs may have beneficial effects on sleep-disordered breathing and OSA through weight loss, which can lead to a reduction in excess adipose tissue, and improvements in metabolic parameters. In terms of studies, a 2023 paper addressed this question, but more research is needed.

Audience member: Is it within a psychiatric provider’s scope of practice to prescribe GLP-1 agents for the reduction of weight gain associated with psychiatric medications?

TI-M: Obesity medicine is an interdisciplinary process. Numerous medications prescribed for mental health can contribute to obesity, and psychiatrists can play a role in collaborating with a patient’s primary care provider and/or obesity medicine specialist to determine which medications can be adjusted or replaced. It is important to remember that obesity management is not just about medications. It requires managing nutrition and activity in addition to behavioral health issues and social determinants of health. If the clinician has had the training to manage these pillars and is comfortable managing this chronic illness — similar to diabetes, hypertension, and other conditions — then this is a possibility. Otherwise, team-based care is appropriate.

Holly Lofton, MD, obesity medicine, NYU Langone Health, New York City

Audience member: Can we safely use them on patients who have had bariatric surgery and regularly develop dumping syndrome?

HL: These medications can be used after bariatric surgery in patients who meet the criteria for pharmacologic treatment. If a patient is having postoperative symptoms of dumping syndrome or excessive gastrointestinal losses from vomiting or diarrhea, dietary adjustments and other methods of managing the dumping syndrome in gastric bypass patients should be initiated before considering GLP-1 RAs because these patients do not have a functioning pylorus in their alimentary tract and these drugs are not indicated to treat dumping syndrome. The first-line approach typically involves reducing the patient’s intake of simple carbohydrates but can also include medications or surgical intervention when appropriate.

Audience member: Would teaching a patient to fast intermittently while they’re on GLP-1 RAs help them preserve weight loss if they choose to wean off the medication?

HL: Personally, I feel it is best to use the titration period and the time in which the patient is actively losing weight when on GLP-1 RAs. These are the best periods to help develop an individualized treatment plan, one that includes nutrition, activity, behavior modification, and resistance training. The patient’s lifestyle plan will likely change based on their environment and other factors. Intermittent fasting can be a part of such a plan. There is no consensus as to exactly which eating pattern will help patients maintain weight once they lose the physiologic benefit of the weight loss medications. However, studies have been published that demonstrate an average weight regain of 66% or greater when patients go from taking the maximum dose of a GLP-1 RA to taking none at all. Thus, patients should still be followed closely for weight regain when they discontinue a GLP-1 RA.

A version of this article appeared on Medscape.com.

The arrival of GLP-1 receptor agonists has revolutionized treatment options for people with obesity and medical practice.

This news organization recently hosted a panel of experts across specialties — including endocrinology, gastroenterology, and obesity medicine — to discuss these potentially life-changing medications and to answer questions from the audience.

Because of the flood of queries from our audience, we asked our panelists to address some of the questions that didn’t make the recording. Their answers are below.

Beverly Tchang, MD, endocrinologist, Weill Cornell Medicine, New York City

Audience member: Can you initiate glucagon-like peptide-1 agonists (GLP-1 RAs) as a primary drug in a patient with obesity and newly diagnosed type 2 diabetes?

BT: We often prescribe GLP-1 RAs to individuals with type 2 diabetes as a first-line medication. Guidelines from the American Diabetes Association are really emphasizing a patient-centered approach, and metformin may not be the best first-line medication anymore.

Audience member: What should clinicians know about dose titration of GLP-1 RAs in diabetic patients with renal disease, especially those in stages IV and V chronic kidney disease?

BT: GLP-1 RAs do not need to be renally dosed, but I still recommend conferring with the patient’s nephrologist because the glomerular filtration rate might decrease in the setting of dehydration. Because GLP1s suppress the thirst, not just appetite, patients can go all day without drinking water and not feel thirsty.

Michael Camilleri, MD, gastroenterologist, Mayo Clinic, Rochester, Minnesota

Audience member: Should GLP-1 RAs be held for 1 week or 4 weeks prior to surgery to reduce the patient’s risk for aspiration? And is tapering required?

MC: For a patient taking liraglutide, I would hold the drug for 1 week prior to surgery. For patients taking other GLP-1 RAs, including extended exenatide, I advise holding for between 2 and 3 weeks before the procedure. It’s also important to make sure the patient’s diabetes is well-controlled with other medications — not GLP-1 RAs — during this period.

After surgery, you can restart GLP-1 RA therapy once there is recovery of oral food intake and normal bowel function.

Audience member: Is treatment with GLP-1 RAs appropriate for a patient with a family history of colon cancer but an otherwise unremarkable medical and family history?

MC: I have not seen a contraindication to receiving GLP-1 RAs based on a family history of colorectal cancer or other malignancies. An analysis of the French national healthcare insurance system database has suggested 1-3 years use of GLP-1 RAs (exenatide, liraglutide, and dulaglutide) may be linked with increased occurrence of thyroid cancer. Data from 37 randomized controlled trials and 19 real-world studies having 16,839 patients in placebo control group, 16,550 patients in active control group, and 13,330 patients in real-world studies were analyzed in a 2023 systematic review and meta-analysis. Compared to placebo or active control treatments, occurrence of pancreatic cancer, thyroid cancer, and all neoplasms — benign, malignant, and otherwise unspecified — were similar in the semaglutide group.

Toshi Iroku-Malize, MD, MPH, MBA, FAAFP, family physician, Zucker School of Medicine, Hempstead, New York

Audience member: What do you do about elevated liver functions after starting treatment with GLP-1 RAs, and what do you do when a patient has reached their weight loss goal?

TI-M: I recommend monitoring the liver function tests, evaluating for underlying causes, such as viral hepatitis, alcohol-related damage, or problems with other medications, and consulting a gastroenterologist or liver specialist if necessary. It’s also important to discuss the risk-benefit of continuing on the GP-1 RA for that particular patient.

Audience member: What effects will GLP-1 RAs have on sleep-disordered breathing/obstructive sleep apnea (OSA)? Are you aware of any ongoing trials addressing this subject?

TI-M: GLP-1 RAs may have beneficial effects on sleep-disordered breathing and OSA through weight loss, which can lead to a reduction in excess adipose tissue, and improvements in metabolic parameters. In terms of studies, a 2023 paper addressed this question, but more research is needed.

Audience member: Is it within a psychiatric provider’s scope of practice to prescribe GLP-1 agents for the reduction of weight gain associated with psychiatric medications?

TI-M: Obesity medicine is an interdisciplinary process. Numerous medications prescribed for mental health can contribute to obesity, and psychiatrists can play a role in collaborating with a patient’s primary care provider and/or obesity medicine specialist to determine which medications can be adjusted or replaced. It is important to remember that obesity management is not just about medications. It requires managing nutrition and activity in addition to behavioral health issues and social determinants of health. If the clinician has had the training to manage these pillars and is comfortable managing this chronic illness — similar to diabetes, hypertension, and other conditions — then this is a possibility. Otherwise, team-based care is appropriate.

Holly Lofton, MD, obesity medicine, NYU Langone Health, New York City

Audience member: Can we safely use them on patients who have had bariatric surgery and regularly develop dumping syndrome?

HL: These medications can be used after bariatric surgery in patients who meet the criteria for pharmacologic treatment. If a patient is having postoperative symptoms of dumping syndrome or excessive gastrointestinal losses from vomiting or diarrhea, dietary adjustments and other methods of managing the dumping syndrome in gastric bypass patients should be initiated before considering GLP-1 RAs because these patients do not have a functioning pylorus in their alimentary tract and these drugs are not indicated to treat dumping syndrome. The first-line approach typically involves reducing the patient’s intake of simple carbohydrates but can also include medications or surgical intervention when appropriate.

Audience member: Would teaching a patient to fast intermittently while they’re on GLP-1 RAs help them preserve weight loss if they choose to wean off the medication?

HL: Personally, I feel it is best to use the titration period and the time in which the patient is actively losing weight when on GLP-1 RAs. These are the best periods to help develop an individualized treatment plan, one that includes nutrition, activity, behavior modification, and resistance training. The patient’s lifestyle plan will likely change based on their environment and other factors. Intermittent fasting can be a part of such a plan. There is no consensus as to exactly which eating pattern will help patients maintain weight once they lose the physiologic benefit of the weight loss medications. However, studies have been published that demonstrate an average weight regain of 66% or greater when patients go from taking the maximum dose of a GLP-1 RA to taking none at all. Thus, patients should still be followed closely for weight regain when they discontinue a GLP-1 RA.

A version of this article appeared on Medscape.com.

The arrival of GLP-1 receptor agonists has revolutionized treatment options for people with obesity and medical practice.

This news organization recently hosted a panel of experts across specialties — including endocrinology, gastroenterology, and obesity medicine — to discuss these potentially life-changing medications and to answer questions from the audience.

Because of the flood of queries from our audience, we asked our panelists to address some of the questions that didn’t make the recording. Their answers are below.

Beverly Tchang, MD, endocrinologist, Weill Cornell Medicine, New York City

Audience member: Can you initiate glucagon-like peptide-1 agonists (GLP-1 RAs) as a primary drug in a patient with obesity and newly diagnosed type 2 diabetes?

BT: We often prescribe GLP-1 RAs to individuals with type 2 diabetes as a first-line medication. Guidelines from the American Diabetes Association are really emphasizing a patient-centered approach, and metformin may not be the best first-line medication anymore.

Audience member: What should clinicians know about dose titration of GLP-1 RAs in diabetic patients with renal disease, especially those in stages IV and V chronic kidney disease?

BT: GLP-1 RAs do not need to be renally dosed, but I still recommend conferring with the patient’s nephrologist because the glomerular filtration rate might decrease in the setting of dehydration. Because GLP1s suppress the thirst, not just appetite, patients can go all day without drinking water and not feel thirsty.

Michael Camilleri, MD, gastroenterologist, Mayo Clinic, Rochester, Minnesota

Audience member: Should GLP-1 RAs be held for 1 week or 4 weeks prior to surgery to reduce the patient’s risk for aspiration? And is tapering required?

MC: For a patient taking liraglutide, I would hold the drug for 1 week prior to surgery. For patients taking other GLP-1 RAs, including extended exenatide, I advise holding for between 2 and 3 weeks before the procedure. It’s also important to make sure the patient’s diabetes is well-controlled with other medications — not GLP-1 RAs — during this period.

After surgery, you can restart GLP-1 RA therapy once there is recovery of oral food intake and normal bowel function.

Audience member: Is treatment with GLP-1 RAs appropriate for a patient with a family history of colon cancer but an otherwise unremarkable medical and family history?

MC: I have not seen a contraindication to receiving GLP-1 RAs based on a family history of colorectal cancer or other malignancies. An analysis of the French national healthcare insurance system database has suggested 1-3 years use of GLP-1 RAs (exenatide, liraglutide, and dulaglutide) may be linked with increased occurrence of thyroid cancer. Data from 37 randomized controlled trials and 19 real-world studies having 16,839 patients in placebo control group, 16,550 patients in active control group, and 13,330 patients in real-world studies were analyzed in a 2023 systematic review and meta-analysis. Compared to placebo or active control treatments, occurrence of pancreatic cancer, thyroid cancer, and all neoplasms — benign, malignant, and otherwise unspecified — were similar in the semaglutide group.

Toshi Iroku-Malize, MD, MPH, MBA, FAAFP, family physician, Zucker School of Medicine, Hempstead, New York

Audience member: What do you do about elevated liver functions after starting treatment with GLP-1 RAs, and what do you do when a patient has reached their weight loss goal?

TI-M: I recommend monitoring the liver function tests, evaluating for underlying causes, such as viral hepatitis, alcohol-related damage, or problems with other medications, and consulting a gastroenterologist or liver specialist if necessary. It’s also important to discuss the risk-benefit of continuing on the GP-1 RA for that particular patient.

Audience member: What effects will GLP-1 RAs have on sleep-disordered breathing/obstructive sleep apnea (OSA)? Are you aware of any ongoing trials addressing this subject?

TI-M: GLP-1 RAs may have beneficial effects on sleep-disordered breathing and OSA through weight loss, which can lead to a reduction in excess adipose tissue, and improvements in metabolic parameters. In terms of studies, a 2023 paper addressed this question, but more research is needed.

Audience member: Is it within a psychiatric provider’s scope of practice to prescribe GLP-1 agents for the reduction of weight gain associated with psychiatric medications?

TI-M: Obesity medicine is an interdisciplinary process. Numerous medications prescribed for mental health can contribute to obesity, and psychiatrists can play a role in collaborating with a patient’s primary care provider and/or obesity medicine specialist to determine which medications can be adjusted or replaced. It is important to remember that obesity management is not just about medications. It requires managing nutrition and activity in addition to behavioral health issues and social determinants of health. If the clinician has had the training to manage these pillars and is comfortable managing this chronic illness — similar to diabetes, hypertension, and other conditions — then this is a possibility. Otherwise, team-based care is appropriate.

Holly Lofton, MD, obesity medicine, NYU Langone Health, New York City

Audience member: Can we safely use them on patients who have had bariatric surgery and regularly develop dumping syndrome?

HL: These medications can be used after bariatric surgery in patients who meet the criteria for pharmacologic treatment. If a patient is having postoperative symptoms of dumping syndrome or excessive gastrointestinal losses from vomiting or diarrhea, dietary adjustments and other methods of managing the dumping syndrome in gastric bypass patients should be initiated before considering GLP-1 RAs because these patients do not have a functioning pylorus in their alimentary tract and these drugs are not indicated to treat dumping syndrome. The first-line approach typically involves reducing the patient’s intake of simple carbohydrates but can also include medications or surgical intervention when appropriate.

Audience member: Would teaching a patient to fast intermittently while they’re on GLP-1 RAs help them preserve weight loss if they choose to wean off the medication?

HL: Personally, I feel it is best to use the titration period and the time in which the patient is actively losing weight when on GLP-1 RAs. These are the best periods to help develop an individualized treatment plan, one that includes nutrition, activity, behavior modification, and resistance training. The patient’s lifestyle plan will likely change based on their environment and other factors. Intermittent fasting can be a part of such a plan. There is no consensus as to exactly which eating pattern will help patients maintain weight once they lose the physiologic benefit of the weight loss medications. However, studies have been published that demonstrate an average weight regain of 66% or greater when patients go from taking the maximum dose of a GLP-1 RA to taking none at all. Thus, patients should still be followed closely for weight regain when they discontinue a GLP-1 RA.

A version of this article appeared on Medscape.com.

People with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2) inhibitors show a significantly reduced risk of developing kidney stones compared with those treated with other commonly used diabetes drugs.

“To our knowledge, this study is the first and largest to assess the association between SGLT2 inhibitors use and risk of nephrolithiasis [kidney stones] in patients with type 2 diabetes in routine US clinical practice,” said the authors of the study, published in JAMA Internal Medicine. 

“Our results suggest that for patients with type 2 diabetes, the individual risk profile for developing nephrolithiasis could be a consideration when deciding which glucose-lowering agent patients should initiate,” they wrote.

The prevalence of kidney stones has been on the rise, and the problem is especially relevant to those with type 2 diabetes, which is known to have an increased risk of kidney stones, potentially causing severe pain and leading to kidney function decline.

With SGLT2 inhibitors showing renoprotective, in addition to cardiovascular benefits, first author Julie Paik, MD, MPH, an associate professor of medicine in the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney) Medicine at Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues conducted an active comparator cohort study using data from three nationwide databases on patients with type 2 diabetes in routine clinical practice.

In the study’s two arms of propensity score-matched patients, 358,203 pairs of patients with type 2 diabetes were matched 1:1 to either those who were new users of SGLT2 inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), with patients in those groups having a mean age of 61 and being about 51% female.

In addition, 331,028 pairs matched new SGLT2 inhibitor users 1:1 with didpeptidyl peptidase-4 (DPP4) inhibitor users, who also had a mean age of about 61.5 years and were about 47% female.

Over a median follow-up of 192 days, those treated with SGLT2 inhibitors had about a 31% significantly lower risk of kidney stones than GLP-1RA users (14.9 vs 21.3 events per 1000 person-years; hazard ratio [HR], 0.69).

And the SGLT2 group also had a 26% lower kidney stone risk vs DPP4 inhibitor users (14.6 vs 19.9 events per 1000 person-years; HR, 0.74).

There were no differences in the results with either groups of pairs based on sex, race, ethnicity, a history of chronic kidney disease, or obesity.

Of note, the magnitude of the risk reduction observed with SGLT2 inhibitors was greater in adults aged < 70 years than in those aged ≥ 70 years (HR, 0.85; P for interaction < .001).

The age-related difference could possibly be due to changes in stone composition that occurs with aging, which may influence SGLT2 inhibitor response, Dr Paik told this news organization.

“However, we did not have information on stone composition in our study.”

In the study, patients were taking, on average, more than two antidiabetic medications upon entrance to the study, with 13% taking thiazides and 12% taking loop diuretics. In addition, approximately half of patients discontinued SGLT2 inhibitors (52.6%) and DPP4 inhibitors (53.2%).

However, the results remained consistent after adjusting for those factors, Dr. Paik noted.
 

Mechanisms: Urinary Citrate Excretion?

Among key possible explanations for the lower risk of kidney stones with SGLT2 inhibitors is that the drugs have increased urinary citrate excretion, with one study showing a nearly 50% increase in urinary citrate excretion among patients treated with empagliflozin vs placebo over 4 weeks and other studies also showing similar increases.

“This increased urinary citrate excretion may play a pivotal role in decreasing stone risk by inhibiting supersaturation and crystallization of calcium crystals,” the authors explained.

In addition, the urinary citrate excretion could further play a role by “forming complexes with calcium and thus lowering urinary calcium concentration, and raising urinary pH, thereby reducing the risk of uric acid stones,” they added.

SGLT inhibitors’ anti-inflammatory effects could also reduce stone formation by “suppressing the expression of a stone core matrix protein, osteopontin, and markers of kidney injury, inflammation, and macrophages that promote stone formation,” the authors noted.

Ultimately, however, “while we found a lower risk of kidney stones in our study, we don’t fully understand how they lower the risk,” Dr. Paik said. The potential explanations “remain to be studied further.”

Either way, “the risk of kidney stones in a patient might be one additional consideration for a clinician to take into account when choosing among the different glucose-lowering agents for patients with type 2 diabetes,” Dr. Paik said.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, the National Institute of Aging the Patient-Centered Outcomes Research Institute, the US Food and Drug Administration, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

A version of this article appeared on Medscape.com .

People with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2) inhibitors show a significantly reduced risk of developing kidney stones compared with those treated with other commonly used diabetes drugs.

“To our knowledge, this study is the first and largest to assess the association between SGLT2 inhibitors use and risk of nephrolithiasis [kidney stones] in patients with type 2 diabetes in routine US clinical practice,” said the authors of the study, published in JAMA Internal Medicine. 

“Our results suggest that for patients with type 2 diabetes, the individual risk profile for developing nephrolithiasis could be a consideration when deciding which glucose-lowering agent patients should initiate,” they wrote.

The prevalence of kidney stones has been on the rise, and the problem is especially relevant to those with type 2 diabetes, which is known to have an increased risk of kidney stones, potentially causing severe pain and leading to kidney function decline.

With SGLT2 inhibitors showing renoprotective, in addition to cardiovascular benefits, first author Julie Paik, MD, MPH, an associate professor of medicine in the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney) Medicine at Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues conducted an active comparator cohort study using data from three nationwide databases on patients with type 2 diabetes in routine clinical practice.

In the study’s two arms of propensity score-matched patients, 358,203 pairs of patients with type 2 diabetes were matched 1:1 to either those who were new users of SGLT2 inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), with patients in those groups having a mean age of 61 and being about 51% female.

In addition, 331,028 pairs matched new SGLT2 inhibitor users 1:1 with didpeptidyl peptidase-4 (DPP4) inhibitor users, who also had a mean age of about 61.5 years and were about 47% female.

Over a median follow-up of 192 days, those treated with SGLT2 inhibitors had about a 31% significantly lower risk of kidney stones than GLP-1RA users (14.9 vs 21.3 events per 1000 person-years; hazard ratio [HR], 0.69).

And the SGLT2 group also had a 26% lower kidney stone risk vs DPP4 inhibitor users (14.6 vs 19.9 events per 1000 person-years; HR, 0.74).

There were no differences in the results with either groups of pairs based on sex, race, ethnicity, a history of chronic kidney disease, or obesity.

Of note, the magnitude of the risk reduction observed with SGLT2 inhibitors was greater in adults aged < 70 years than in those aged ≥ 70 years (HR, 0.85; P for interaction < .001).

The age-related difference could possibly be due to changes in stone composition that occurs with aging, which may influence SGLT2 inhibitor response, Dr Paik told this news organization.

“However, we did not have information on stone composition in our study.”

In the study, patients were taking, on average, more than two antidiabetic medications upon entrance to the study, with 13% taking thiazides and 12% taking loop diuretics. In addition, approximately half of patients discontinued SGLT2 inhibitors (52.6%) and DPP4 inhibitors (53.2%).

However, the results remained consistent after adjusting for those factors, Dr. Paik noted.
 

Mechanisms: Urinary Citrate Excretion?

Among key possible explanations for the lower risk of kidney stones with SGLT2 inhibitors is that the drugs have increased urinary citrate excretion, with one study showing a nearly 50% increase in urinary citrate excretion among patients treated with empagliflozin vs placebo over 4 weeks and other studies also showing similar increases.

“This increased urinary citrate excretion may play a pivotal role in decreasing stone risk by inhibiting supersaturation and crystallization of calcium crystals,” the authors explained.

In addition, the urinary citrate excretion could further play a role by “forming complexes with calcium and thus lowering urinary calcium concentration, and raising urinary pH, thereby reducing the risk of uric acid stones,” they added.

SGLT inhibitors’ anti-inflammatory effects could also reduce stone formation by “suppressing the expression of a stone core matrix protein, osteopontin, and markers of kidney injury, inflammation, and macrophages that promote stone formation,” the authors noted.

Ultimately, however, “while we found a lower risk of kidney stones in our study, we don’t fully understand how they lower the risk,” Dr. Paik said. The potential explanations “remain to be studied further.”

Either way, “the risk of kidney stones in a patient might be one additional consideration for a clinician to take into account when choosing among the different glucose-lowering agents for patients with type 2 diabetes,” Dr. Paik said.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, the National Institute of Aging the Patient-Centered Outcomes Research Institute, the US Food and Drug Administration, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

A version of this article appeared on Medscape.com .

People with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2) inhibitors show a significantly reduced risk of developing kidney stones compared with those treated with other commonly used diabetes drugs.

“To our knowledge, this study is the first and largest to assess the association between SGLT2 inhibitors use and risk of nephrolithiasis [kidney stones] in patients with type 2 diabetes in routine US clinical practice,” said the authors of the study, published in JAMA Internal Medicine. 

“Our results suggest that for patients with type 2 diabetes, the individual risk profile for developing nephrolithiasis could be a consideration when deciding which glucose-lowering agent patients should initiate,” they wrote.

The prevalence of kidney stones has been on the rise, and the problem is especially relevant to those with type 2 diabetes, which is known to have an increased risk of kidney stones, potentially causing severe pain and leading to kidney function decline.

With SGLT2 inhibitors showing renoprotective, in addition to cardiovascular benefits, first author Julie Paik, MD, MPH, an associate professor of medicine in the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney) Medicine at Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues conducted an active comparator cohort study using data from three nationwide databases on patients with type 2 diabetes in routine clinical practice.

In the study’s two arms of propensity score-matched patients, 358,203 pairs of patients with type 2 diabetes were matched 1:1 to either those who were new users of SGLT2 inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), with patients in those groups having a mean age of 61 and being about 51% female.

In addition, 331,028 pairs matched new SGLT2 inhibitor users 1:1 with didpeptidyl peptidase-4 (DPP4) inhibitor users, who also had a mean age of about 61.5 years and were about 47% female.

Over a median follow-up of 192 days, those treated with SGLT2 inhibitors had about a 31% significantly lower risk of kidney stones than GLP-1RA users (14.9 vs 21.3 events per 1000 person-years; hazard ratio [HR], 0.69).

And the SGLT2 group also had a 26% lower kidney stone risk vs DPP4 inhibitor users (14.6 vs 19.9 events per 1000 person-years; HR, 0.74).

There were no differences in the results with either groups of pairs based on sex, race, ethnicity, a history of chronic kidney disease, or obesity.

Of note, the magnitude of the risk reduction observed with SGLT2 inhibitors was greater in adults aged < 70 years than in those aged ≥ 70 years (HR, 0.85; P for interaction < .001).

The age-related difference could possibly be due to changes in stone composition that occurs with aging, which may influence SGLT2 inhibitor response, Dr Paik told this news organization.

“However, we did not have information on stone composition in our study.”

In the study, patients were taking, on average, more than two antidiabetic medications upon entrance to the study, with 13% taking thiazides and 12% taking loop diuretics. In addition, approximately half of patients discontinued SGLT2 inhibitors (52.6%) and DPP4 inhibitors (53.2%).

However, the results remained consistent after adjusting for those factors, Dr. Paik noted.
 

Mechanisms: Urinary Citrate Excretion?

Among key possible explanations for the lower risk of kidney stones with SGLT2 inhibitors is that the drugs have increased urinary citrate excretion, with one study showing a nearly 50% increase in urinary citrate excretion among patients treated with empagliflozin vs placebo over 4 weeks and other studies also showing similar increases.

“This increased urinary citrate excretion may play a pivotal role in decreasing stone risk by inhibiting supersaturation and crystallization of calcium crystals,” the authors explained.

In addition, the urinary citrate excretion could further play a role by “forming complexes with calcium and thus lowering urinary calcium concentration, and raising urinary pH, thereby reducing the risk of uric acid stones,” they added.

SGLT inhibitors’ anti-inflammatory effects could also reduce stone formation by “suppressing the expression of a stone core matrix protein, osteopontin, and markers of kidney injury, inflammation, and macrophages that promote stone formation,” the authors noted.

Ultimately, however, “while we found a lower risk of kidney stones in our study, we don’t fully understand how they lower the risk,” Dr. Paik said. The potential explanations “remain to be studied further.”

Either way, “the risk of kidney stones in a patient might be one additional consideration for a clinician to take into account when choosing among the different glucose-lowering agents for patients with type 2 diabetes,” Dr. Paik said.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, the National Institute of Aging the Patient-Centered Outcomes Research Institute, the US Food and Drug Administration, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

A version of this article appeared on Medscape.com .

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.