Diabetes

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

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 first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

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 first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

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 first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

A version of this article first appeared on Medscape.com.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

A version of this article first appeared on Medscape.com.

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

A version of this article first appeared on Medscape.com.

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

A version of this article first appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.