Obesity

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

This transcript has been edited for clarity.

Akshay B. Jain, MD: Welcome back to Medscape at ADA 2024, where Dr. James Kim, primary care physician from Calgary, Alberta, will be joining me in deciphering the key highlights at the ADA conference and bringing our own clinical twist into what the relevance would be for people like you and I to take back to our clinics.

Welcome back, Dr. Kim. 

James Kim, MBBCh, PgDip, MScCH: Thank you very much. It’s nice to be back. 

Dr. Jain: This was a diabetes conference, so obviously we are very pancreas focused. At this conference, we went outside our general area of territory, going outside of the pancreas and delving into other organ states. What I found fascinating were some data regarding the effects of incretin therapy on the lung, and in particular, some of the restrictive lung disorders.

Dr. Kim, you attended these sessions as well. Can you tell us a little bit more about the results that were discussed? 

Dr. Kim: This is an interesting field. The moderator of the session went up and said that there has been no time in any previous ADA sessions where the lung issue was actually discussed. This was the first time ever.

They had some of the world leaders in this field, so it was really awesome to see them. Just to paint a picture of these obese asthmatic patients, they are challenging cases because, as you know, the main therapy for any asthmatic patient is inhaled corticosteroid.

Patients who are obese have quite a bit of a steroid resistance. Therefore, they end up being on many medications that sometimes are off label, and many end up on biologics as well. Therefore, the respiratory world has been seeking therapies for these obese asthmatic patients who are likely to be steroid resistant because these people are also likely to end up on an oral steroid as well.

Dr. Jain, you know the effect of the steroids much better than I do, and it’s like a laundry list. We really don’t want our patients to be on oral steroids. 

In the past few years, GLP-1 has been studied quite extensively in the lung, especially in the world of asthma, and also in COPD. What’s really fascinating is that the GLP-1 receptors have been found to be quite abundant in the airway. Some studies show that the highest concentration of GLP-1 lies in the airway, whereas some studies have said that it’s the third most common area to find the GLP-1. 

It is not a surprise that GLP-1 is being studied in managing the airway, especially airway inflammation in asthma and COPD patients. The preliminary data have been quite encouraging. They also discussed that there are new medications coming out that seem to be incretin based, so we’ll wait to see what those studies show.

There are two current phase 3 trials being held at the moment. One is using semaglutide 2.4 mg subcutaneous and another one is using metformin to reduce the airway inflammation in these asthmatic patients and also in some COPD patients. We’ll look forward to these results.

Dr. Jain: That’s really important to note because we see that there is a high density of these receptors in the airways, and hitherto we had no idea about the overall effect. Now, we’re looking at, as you mentioned, individuals with obesity who have asthma, so there are both the restrictive and obstructive components in the lung coming into play here.

From an endocrinology perspective, I’m thinking that this could be multiple effects of the GLP-1 receptor agonists, where on one hand you’re managing the obesity and you’re working along that line, and on the other hand, it could have local anti-inflammatory effects in the lung. Hence, there could be potential improvement in the overall pulmonary function of these individuals. 

Dr. Kim: We are seeing this in primary care. Ever since I found out this information, I have started numerous patients, who are obese, asthmatic patients who do not have diabetes, on GLP-1 therapies, and their pulmonary function tests have improved significantly.

As a matter of fact, one of my personal friends is a severe asthmatic patient. She ends up being on oral steroids about three times a year. There was even one day when I saw her in one of my classes and she was dyspneic. She was short of breath. 

I introduced her to one of my colleagues who’s a respirologist and very much into the impact of the incretins and asthma, and she was started on a GLP-1 receptor agonist. She lost about 30 pounds of weight, but now she is labeled as a mild asthmatic. Her pulmonary function test is completely normal. She hasn’t touched an oral steroid for a couple of years now.

That is a huge success story and I’m seeing that even in my own clinic as well. It’s a huge win for the respiratory world.

Dr. Jain: I think from an endocrinology perspective as well, if we are initiating GLP-1 receptor agonists or medications in that class, where we use it for management of obesity, sooner or later we do hit a stage where people will plateau with their weight loss. They won’t have any additional weight loss.

We tell individuals at that time that the fact that they’re able to maintain the weight loss still means that the medication is working from the obesity perspective. For individuals who also have asthma, it would be a good point to tell them that it could still have potential effects on reducing inflammation ongoing. Hence, even though they may not be losing any additional weight, it would still be helpful to continue on these medications from a pulmonary perspective. 

Dr. Kim: Right now these pleiotropic effects of GLP-1 agents are absolutely mind-blowing. I mentioned in one of my respiratory presentations to a bunch of respirologists that diabetes is taking over the world, including the respiratory world. Well, you can imagine what their faces were like. However, they were quite impressed at that, and they were very excited with what these two phase 3 trials will show. 

Dr. Jain: I think, based on the ADA 2024 conference, GLP-1 receptor agonists continue to be the gift that keeps giving. We have the effects on diabetes, obesity, kidney function, liver protection, lungs, and Alzheimer’s. We saw some sessions about potential use in people with alcohol misuse disorder or gambling problems. Clearly, there’s a large amount of research that›s being done with these agents. 

Perhaps when you and I talk about ADA 2025, we might be able to talk about some more pleiotropic benefits outside the pancreas. Until then, please do check out our other videos from ADA 2024. Thanks for joining us again, Dr. Kim.

Dr. Kim: Thank you very much for having me.
 

Dr. Jain, clinical instructor, Department of Endocrinology, University of British Columbia, and endocrinologist, TLC Diabetes and Endocrinology, Vancouver, British Columbia, Canada, has disclosed ties with Abbott, Acerus, AstraZeneca, Amgen, Bausch Healthcare, Bayer, Boehringer Ingelheim, Care to Know, CCRN, Connected in Motion, CPD Network, Dexcom, Diabetes Canada, Eli Lilly, GSK, HLS Therapeutics, Janssen, Master Clinician Alliance, MDBriefcase, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Partners in Progressive Medical Education, Pfizer, Sanofi Aventis, Timed Right, WebMD, Gilead Sciences, Insulet, PocketPills, Roche, and Takeda. Dr. Kim, clinical assistant professor, Department of Family Medicine, University of Calgary, Alberta, has disclosed ties with Abbott, AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Embecta, Eli Lilly, GSK, Janssen, Linpharma, Novo Nordisk, Miravo, Otsuka, Pfizer, Teva, Takeda, and Sanofi, and Partners in Progressive Medical Education.
 

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

This transcript has been edited for clarity.

Akshay B. Jain, MD: Welcome back to Medscape at ADA 2024, where Dr. James Kim, primary care physician from Calgary, Alberta, will be joining me in deciphering the key highlights at the ADA conference and bringing our own clinical twist into what the relevance would be for people like you and I to take back to our clinics.

Welcome back, Dr. Kim. 

James Kim, MBBCh, PgDip, MScCH: Thank you very much. It’s nice to be back. 

Dr. Jain: This was a diabetes conference, so obviously we are very pancreas focused. At this conference, we went outside our general area of territory, going outside of the pancreas and delving into other organ states. What I found fascinating were some data regarding the effects of incretin therapy on the lung, and in particular, some of the restrictive lung disorders.

Dr. Kim, you attended these sessions as well. Can you tell us a little bit more about the results that were discussed? 

Dr. Kim: This is an interesting field. The moderator of the session went up and said that there has been no time in any previous ADA sessions where the lung issue was actually discussed. This was the first time ever.

They had some of the world leaders in this field, so it was really awesome to see them. Just to paint a picture of these obese asthmatic patients, they are challenging cases because, as you know, the main therapy for any asthmatic patient is inhaled corticosteroid.

Patients who are obese have quite a bit of a steroid resistance. Therefore, they end up being on many medications that sometimes are off label, and many end up on biologics as well. Therefore, the respiratory world has been seeking therapies for these obese asthmatic patients who are likely to be steroid resistant because these people are also likely to end up on an oral steroid as well.

Dr. Jain, you know the effect of the steroids much better than I do, and it’s like a laundry list. We really don’t want our patients to be on oral steroids. 

In the past few years, GLP-1 has been studied quite extensively in the lung, especially in the world of asthma, and also in COPD. What’s really fascinating is that the GLP-1 receptors have been found to be quite abundant in the airway. Some studies show that the highest concentration of GLP-1 lies in the airway, whereas some studies have said that it’s the third most common area to find the GLP-1. 

It is not a surprise that GLP-1 is being studied in managing the airway, especially airway inflammation in asthma and COPD patients. The preliminary data have been quite encouraging. They also discussed that there are new medications coming out that seem to be incretin based, so we’ll wait to see what those studies show.

There are two current phase 3 trials being held at the moment. One is using semaglutide 2.4 mg subcutaneous and another one is using metformin to reduce the airway inflammation in these asthmatic patients and also in some COPD patients. We’ll look forward to these results.

Dr. Jain: That’s really important to note because we see that there is a high density of these receptors in the airways, and hitherto we had no idea about the overall effect. Now, we’re looking at, as you mentioned, individuals with obesity who have asthma, so there are both the restrictive and obstructive components in the lung coming into play here.

From an endocrinology perspective, I’m thinking that this could be multiple effects of the GLP-1 receptor agonists, where on one hand you’re managing the obesity and you’re working along that line, and on the other hand, it could have local anti-inflammatory effects in the lung. Hence, there could be potential improvement in the overall pulmonary function of these individuals. 

Dr. Kim: We are seeing this in primary care. Ever since I found out this information, I have started numerous patients, who are obese, asthmatic patients who do not have diabetes, on GLP-1 therapies, and their pulmonary function tests have improved significantly.

As a matter of fact, one of my personal friends is a severe asthmatic patient. She ends up being on oral steroids about three times a year. There was even one day when I saw her in one of my classes and she was dyspneic. She was short of breath. 

I introduced her to one of my colleagues who’s a respirologist and very much into the impact of the incretins and asthma, and she was started on a GLP-1 receptor agonist. She lost about 30 pounds of weight, but now she is labeled as a mild asthmatic. Her pulmonary function test is completely normal. She hasn’t touched an oral steroid for a couple of years now.

That is a huge success story and I’m seeing that even in my own clinic as well. It’s a huge win for the respiratory world.

Dr. Jain: I think from an endocrinology perspective as well, if we are initiating GLP-1 receptor agonists or medications in that class, where we use it for management of obesity, sooner or later we do hit a stage where people will plateau with their weight loss. They won’t have any additional weight loss.

We tell individuals at that time that the fact that they’re able to maintain the weight loss still means that the medication is working from the obesity perspective. For individuals who also have asthma, it would be a good point to tell them that it could still have potential effects on reducing inflammation ongoing. Hence, even though they may not be losing any additional weight, it would still be helpful to continue on these medications from a pulmonary perspective. 

Dr. Kim: Right now these pleiotropic effects of GLP-1 agents are absolutely mind-blowing. I mentioned in one of my respiratory presentations to a bunch of respirologists that diabetes is taking over the world, including the respiratory world. Well, you can imagine what their faces were like. However, they were quite impressed at that, and they were very excited with what these two phase 3 trials will show. 

Dr. Jain: I think, based on the ADA 2024 conference, GLP-1 receptor agonists continue to be the gift that keeps giving. We have the effects on diabetes, obesity, kidney function, liver protection, lungs, and Alzheimer’s. We saw some sessions about potential use in people with alcohol misuse disorder or gambling problems. Clearly, there’s a large amount of research that›s being done with these agents. 

Perhaps when you and I talk about ADA 2025, we might be able to talk about some more pleiotropic benefits outside the pancreas. Until then, please do check out our other videos from ADA 2024. Thanks for joining us again, Dr. Kim.

Dr. Kim: Thank you very much for having me.
 

Dr. Jain, clinical instructor, Department of Endocrinology, University of British Columbia, and endocrinologist, TLC Diabetes and Endocrinology, Vancouver, British Columbia, Canada, has disclosed ties with Abbott, Acerus, AstraZeneca, Amgen, Bausch Healthcare, Bayer, Boehringer Ingelheim, Care to Know, CCRN, Connected in Motion, CPD Network, Dexcom, Diabetes Canada, Eli Lilly, GSK, HLS Therapeutics, Janssen, Master Clinician Alliance, MDBriefcase, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Partners in Progressive Medical Education, Pfizer, Sanofi Aventis, Timed Right, WebMD, Gilead Sciences, Insulet, PocketPills, Roche, and Takeda. Dr. Kim, clinical assistant professor, Department of Family Medicine, University of Calgary, Alberta, has disclosed ties with Abbott, AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Embecta, Eli Lilly, GSK, Janssen, Linpharma, Novo Nordisk, Miravo, Otsuka, Pfizer, Teva, Takeda, and Sanofi, and Partners in Progressive Medical Education.
 

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

This transcript has been edited for clarity.

Akshay B. Jain, MD: Welcome back to Medscape at ADA 2024, where Dr. James Kim, primary care physician from Calgary, Alberta, will be joining me in deciphering the key highlights at the ADA conference and bringing our own clinical twist into what the relevance would be for people like you and I to take back to our clinics.

Welcome back, Dr. Kim. 

James Kim, MBBCh, PgDip, MScCH: Thank you very much. It’s nice to be back. 

Dr. Jain: This was a diabetes conference, so obviously we are very pancreas focused. At this conference, we went outside our general area of territory, going outside of the pancreas and delving into other organ states. What I found fascinating were some data regarding the effects of incretin therapy on the lung, and in particular, some of the restrictive lung disorders.

Dr. Kim, you attended these sessions as well. Can you tell us a little bit more about the results that were discussed? 

Dr. Kim: This is an interesting field. The moderator of the session went up and said that there has been no time in any previous ADA sessions where the lung issue was actually discussed. This was the first time ever.

They had some of the world leaders in this field, so it was really awesome to see them. Just to paint a picture of these obese asthmatic patients, they are challenging cases because, as you know, the main therapy for any asthmatic patient is inhaled corticosteroid.

Patients who are obese have quite a bit of a steroid resistance. Therefore, they end up being on many medications that sometimes are off label, and many end up on biologics as well. Therefore, the respiratory world has been seeking therapies for these obese asthmatic patients who are likely to be steroid resistant because these people are also likely to end up on an oral steroid as well.

Dr. Jain, you know the effect of the steroids much better than I do, and it’s like a laundry list. We really don’t want our patients to be on oral steroids. 

In the past few years, GLP-1 has been studied quite extensively in the lung, especially in the world of asthma, and also in COPD. What’s really fascinating is that the GLP-1 receptors have been found to be quite abundant in the airway. Some studies show that the highest concentration of GLP-1 lies in the airway, whereas some studies have said that it’s the third most common area to find the GLP-1. 

It is not a surprise that GLP-1 is being studied in managing the airway, especially airway inflammation in asthma and COPD patients. The preliminary data have been quite encouraging. They also discussed that there are new medications coming out that seem to be incretin based, so we’ll wait to see what those studies show.

There are two current phase 3 trials being held at the moment. One is using semaglutide 2.4 mg subcutaneous and another one is using metformin to reduce the airway inflammation in these asthmatic patients and also in some COPD patients. We’ll look forward to these results.

Dr. Jain: That’s really important to note because we see that there is a high density of these receptors in the airways, and hitherto we had no idea about the overall effect. Now, we’re looking at, as you mentioned, individuals with obesity who have asthma, so there are both the restrictive and obstructive components in the lung coming into play here.

From an endocrinology perspective, I’m thinking that this could be multiple effects of the GLP-1 receptor agonists, where on one hand you’re managing the obesity and you’re working along that line, and on the other hand, it could have local anti-inflammatory effects in the lung. Hence, there could be potential improvement in the overall pulmonary function of these individuals. 

Dr. Kim: We are seeing this in primary care. Ever since I found out this information, I have started numerous patients, who are obese, asthmatic patients who do not have diabetes, on GLP-1 therapies, and their pulmonary function tests have improved significantly.

As a matter of fact, one of my personal friends is a severe asthmatic patient. She ends up being on oral steroids about three times a year. There was even one day when I saw her in one of my classes and she was dyspneic. She was short of breath. 

I introduced her to one of my colleagues who’s a respirologist and very much into the impact of the incretins and asthma, and she was started on a GLP-1 receptor agonist. She lost about 30 pounds of weight, but now she is labeled as a mild asthmatic. Her pulmonary function test is completely normal. She hasn’t touched an oral steroid for a couple of years now.

That is a huge success story and I’m seeing that even in my own clinic as well. It’s a huge win for the respiratory world.

Dr. Jain: I think from an endocrinology perspective as well, if we are initiating GLP-1 receptor agonists or medications in that class, where we use it for management of obesity, sooner or later we do hit a stage where people will plateau with their weight loss. They won’t have any additional weight loss.

We tell individuals at that time that the fact that they’re able to maintain the weight loss still means that the medication is working from the obesity perspective. For individuals who also have asthma, it would be a good point to tell them that it could still have potential effects on reducing inflammation ongoing. Hence, even though they may not be losing any additional weight, it would still be helpful to continue on these medications from a pulmonary perspective. 

Dr. Kim: Right now these pleiotropic effects of GLP-1 agents are absolutely mind-blowing. I mentioned in one of my respiratory presentations to a bunch of respirologists that diabetes is taking over the world, including the respiratory world. Well, you can imagine what their faces were like. However, they were quite impressed at that, and they were very excited with what these two phase 3 trials will show. 

Dr. Jain: I think, based on the ADA 2024 conference, GLP-1 receptor agonists continue to be the gift that keeps giving. We have the effects on diabetes, obesity, kidney function, liver protection, lungs, and Alzheimer’s. We saw some sessions about potential use in people with alcohol misuse disorder or gambling problems. Clearly, there’s a large amount of research that›s being done with these agents. 

Perhaps when you and I talk about ADA 2025, we might be able to talk about some more pleiotropic benefits outside the pancreas. Until then, please do check out our other videos from ADA 2024. Thanks for joining us again, Dr. Kim.

Dr. Kim: Thank you very much for having me.
 

Dr. Jain, clinical instructor, Department of Endocrinology, University of British Columbia, and endocrinologist, TLC Diabetes and Endocrinology, Vancouver, British Columbia, Canada, has disclosed ties with Abbott, Acerus, AstraZeneca, Amgen, Bausch Healthcare, Bayer, Boehringer Ingelheim, Care to Know, CCRN, Connected in Motion, CPD Network, Dexcom, Diabetes Canada, Eli Lilly, GSK, HLS Therapeutics, Janssen, Master Clinician Alliance, MDBriefcase, Merck, Medtronic, Moderna, Novartis, Novo Nordisk, Partners in Progressive Medical Education, Pfizer, Sanofi Aventis, Timed Right, WebMD, Gilead Sciences, Insulet, PocketPills, Roche, and Takeda. Dr. Kim, clinical assistant professor, Department of Family Medicine, University of Calgary, Alberta, has disclosed ties with Abbott, AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Embecta, Eli Lilly, GSK, Janssen, Linpharma, Novo Nordisk, Miravo, Otsuka, Pfizer, Teva, Takeda, and Sanofi, and Partners in Progressive Medical Education.
 

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Take a look at any of the evidence-based US obesity treatment guidelines. The key criteria for diagnosing overweight and obesity is based on the body mass index (BMI). 

The guidelines also use BMI to stratify care options to decrease cardiovascular risk. For example, persons with BMI ≥30 are classified as having obesity, and antiobesity medications are recommended. Those with BMI ≥ 40 are classified as having severe obesity, and metabolic bariatric surgery may be appropriate. 

But where did these cutoff points for more and less aggressive treatments come from? These BMI cutoffs are based primarily on mortality data collected from large non-Hispanic White populations, without data on potential differences by gender and ethnicity. In fact, by itself, BMI is an incomplete measure of cardiometabolic risk, especially in a multiethnic clinic with all genders represented.

For example, it is certainly true that those with BMI ≥ 30 have more cardiovascular risk factors than those with BMI < 30. But Asian American individuals have more risk factors at lower BMIs than do White or African American individuals likely because of more visceral fat accumulation at lower BMIs.

Besides the variation in gender and ethnicity, BMI does not take the type and location of body fat into consideration. Adipose tissue in visceral or ectopic areas have much higher risks for disease than subcutaneous adipose tissue because of the associated inflammation. Measures such as waist circumference, waist-to-hip ratio, and skinfold measurements aim to capture this aspect but often fall short because of variation in techniques.

BMI does not account for muscle mass either, so fit athletes and bodybuilders can be classified as having obesity by BMI alone. More accurate body fat percent measures, such as dual-energy X-ray absorptiometry or MRI specifically for ectopic fat, are labor intensive, expensive, and not feasible to perform in a busy primary care or endocrinology clinic.
 

Assessing Risks From Obesity Beyond BMI

Clearly, better risk measures than BMI are needed, but until they are available, supplemental clinical tools can aid diagnosis and treatment decisions at obesity medicine specialty centers, endocrinology and diabetes centers, and those centers that focus on the treatment of obesity.

For example, a seca scale can measure percent body fat by bioelectric impedance analysis. This technique also has its limitations, but for persons who are well hydrated, it can be used as a baseline to determine efficacy of behavioral interventions, such as resistance-exercise training and a high-protein diet to protect muscle mass as the patient loses weight.

A lot also can be gleaned from diet and exercise history, social history, family history, and physical exam as well as laboratory analyses. For example, an Asian American patient with a BMI of 26 who has been gaining weight mostly in the abdominal region after age 35 years is likely to have cardiometabolic risk, and a family history can solidify that. An exam can show signs of acanthosis nigricans or an enlarged liver and generous abdominal adipose tissue. This would be the patient in whom you would want to obtain a hemoglobin A1c measurement in the chance that it is elevated at > 5.7 mg/dL, suggesting high risk for type 2 diabetes. 

A Fibrosis-4 score can assess the risk for liver disease from aspartate transaminase and alanine aminotransferase and platelet count and age, providing clues to cardiometabolic disease risk.

In the next 10, years there may be a better measure for cardiometabolic risk that is more accurate than BMI is. It could be the sagittal abdominal diameter, which has been purported to more accurately measure visceral abdominal fat. But this has not made it to be one of the vital signs in a busy primary care clinic, however. 
 

Will New Body Fat Tools Change Practice?

In the next 10 years, there may be an affordable gadget to scan the body to determine visceral vs subcutaneous deposition of fat — like radiography for tissue. Now, three-dimensional (3D) total-body scanners can obtain body composition, but they are extremely expensive. The more important clinical question is: How will the use of these imaging modalities change your practice protocol for a particular patient? 

Think about the FibroScan, a type of ultrasound used to determine fatty liver disease and fibrosis. We order the test for those patients in whom we already have a strong suspicion for liver disease and, in obesity practices, for fatty liver and metabolic-associated fatty liver disease or metabolic associated steatohepatitis.

The test results do much to educate the patient and help the patient understand the need for aggressive treatment for their obesity. But it doesn’t necessarily change the clinician’s practice protocols and decisions. We would still recommend weight management and medications or surgery to patients regardless of the findings. 

A FibroScan is an expense, and not all primary care or endocrine practitioners may feel it necessary to purchase one for the added benefit of patient education. And I would argue that a 3D body scanner is a great tool but more for educational purposes than to really determine practice decision-making or outcomes. 

In the meantime, an old-fashioned physical examination, along with a thorough medical, social, and family history should give even the busiest primary care provider enough information to decide whether their patient is a candidate for preventive measures to reduce body fat with diet, exercise, and medication as well as whether the patient is a candidate for metabolic bariatric surgery. Higher suspicion of cardiovascular risk at lower BMI ranges for various ethnicities can help primary care providers pick up on the patients with low BMI but who are at higher risk for type 2 diabetes or prediabetes and cardiovascular disease. 

So the answer to whether we need a better measure than the BMI: Yes, we do. We need a physical examination on all patients.

Dr. Apovian, professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, both in Boston, Massachusetts, disclosed ties with Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, L-Nutra, NeuroBo Pharm, Novo, OptumRx, Pain Script, Palatin, Pursuit by You, Roman Health, Xeno, and Riverview School.

A version of this article appeared on Medscape.com.

Take a look at any of the evidence-based US obesity treatment guidelines. The key criteria for diagnosing overweight and obesity is based on the body mass index (BMI). 

The guidelines also use BMI to stratify care options to decrease cardiovascular risk. For example, persons with BMI ≥30 are classified as having obesity, and antiobesity medications are recommended. Those with BMI ≥ 40 are classified as having severe obesity, and metabolic bariatric surgery may be appropriate. 

But where did these cutoff points for more and less aggressive treatments come from? These BMI cutoffs are based primarily on mortality data collected from large non-Hispanic White populations, without data on potential differences by gender and ethnicity. In fact, by itself, BMI is an incomplete measure of cardiometabolic risk, especially in a multiethnic clinic with all genders represented.

For example, it is certainly true that those with BMI ≥ 30 have more cardiovascular risk factors than those with BMI < 30. But Asian American individuals have more risk factors at lower BMIs than do White or African American individuals likely because of more visceral fat accumulation at lower BMIs.

Besides the variation in gender and ethnicity, BMI does not take the type and location of body fat into consideration. Adipose tissue in visceral or ectopic areas have much higher risks for disease than subcutaneous adipose tissue because of the associated inflammation. Measures such as waist circumference, waist-to-hip ratio, and skinfold measurements aim to capture this aspect but often fall short because of variation in techniques.

BMI does not account for muscle mass either, so fit athletes and bodybuilders can be classified as having obesity by BMI alone. More accurate body fat percent measures, such as dual-energy X-ray absorptiometry or MRI specifically for ectopic fat, are labor intensive, expensive, and not feasible to perform in a busy primary care or endocrinology clinic.
 

Assessing Risks From Obesity Beyond BMI

Clearly, better risk measures than BMI are needed, but until they are available, supplemental clinical tools can aid diagnosis and treatment decisions at obesity medicine specialty centers, endocrinology and diabetes centers, and those centers that focus on the treatment of obesity.

For example, a seca scale can measure percent body fat by bioelectric impedance analysis. This technique also has its limitations, but for persons who are well hydrated, it can be used as a baseline to determine efficacy of behavioral interventions, such as resistance-exercise training and a high-protein diet to protect muscle mass as the patient loses weight.

A lot also can be gleaned from diet and exercise history, social history, family history, and physical exam as well as laboratory analyses. For example, an Asian American patient with a BMI of 26 who has been gaining weight mostly in the abdominal region after age 35 years is likely to have cardiometabolic risk, and a family history can solidify that. An exam can show signs of acanthosis nigricans or an enlarged liver and generous abdominal adipose tissue. This would be the patient in whom you would want to obtain a hemoglobin A1c measurement in the chance that it is elevated at > 5.7 mg/dL, suggesting high risk for type 2 diabetes. 

A Fibrosis-4 score can assess the risk for liver disease from aspartate transaminase and alanine aminotransferase and platelet count and age, providing clues to cardiometabolic disease risk.

In the next 10, years there may be a better measure for cardiometabolic risk that is more accurate than BMI is. It could be the sagittal abdominal diameter, which has been purported to more accurately measure visceral abdominal fat. But this has not made it to be one of the vital signs in a busy primary care clinic, however. 
 

Will New Body Fat Tools Change Practice?

In the next 10 years, there may be an affordable gadget to scan the body to determine visceral vs subcutaneous deposition of fat — like radiography for tissue. Now, three-dimensional (3D) total-body scanners can obtain body composition, but they are extremely expensive. The more important clinical question is: How will the use of these imaging modalities change your practice protocol for a particular patient? 

Think about the FibroScan, a type of ultrasound used to determine fatty liver disease and fibrosis. We order the test for those patients in whom we already have a strong suspicion for liver disease and, in obesity practices, for fatty liver and metabolic-associated fatty liver disease or metabolic associated steatohepatitis.

The test results do much to educate the patient and help the patient understand the need for aggressive treatment for their obesity. But it doesn’t necessarily change the clinician’s practice protocols and decisions. We would still recommend weight management and medications or surgery to patients regardless of the findings. 

A FibroScan is an expense, and not all primary care or endocrine practitioners may feel it necessary to purchase one for the added benefit of patient education. And I would argue that a 3D body scanner is a great tool but more for educational purposes than to really determine practice decision-making or outcomes. 

In the meantime, an old-fashioned physical examination, along with a thorough medical, social, and family history should give even the busiest primary care provider enough information to decide whether their patient is a candidate for preventive measures to reduce body fat with diet, exercise, and medication as well as whether the patient is a candidate for metabolic bariatric surgery. Higher suspicion of cardiovascular risk at lower BMI ranges for various ethnicities can help primary care providers pick up on the patients with low BMI but who are at higher risk for type 2 diabetes or prediabetes and cardiovascular disease. 

So the answer to whether we need a better measure than the BMI: Yes, we do. We need a physical examination on all patients.

Dr. Apovian, professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, both in Boston, Massachusetts, disclosed ties with Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, L-Nutra, NeuroBo Pharm, Novo, OptumRx, Pain Script, Palatin, Pursuit by You, Roman Health, Xeno, and Riverview School.

A version of this article appeared on Medscape.com.

Take a look at any of the evidence-based US obesity treatment guidelines. The key criteria for diagnosing overweight and obesity is based on the body mass index (BMI). 

The guidelines also use BMI to stratify care options to decrease cardiovascular risk. For example, persons with BMI ≥30 are classified as having obesity, and antiobesity medications are recommended. Those with BMI ≥ 40 are classified as having severe obesity, and metabolic bariatric surgery may be appropriate. 

But where did these cutoff points for more and less aggressive treatments come from? These BMI cutoffs are based primarily on mortality data collected from large non-Hispanic White populations, without data on potential differences by gender and ethnicity. In fact, by itself, BMI is an incomplete measure of cardiometabolic risk, especially in a multiethnic clinic with all genders represented.

For example, it is certainly true that those with BMI ≥ 30 have more cardiovascular risk factors than those with BMI < 30. But Asian American individuals have more risk factors at lower BMIs than do White or African American individuals likely because of more visceral fat accumulation at lower BMIs.

Besides the variation in gender and ethnicity, BMI does not take the type and location of body fat into consideration. Adipose tissue in visceral or ectopic areas have much higher risks for disease than subcutaneous adipose tissue because of the associated inflammation. Measures such as waist circumference, waist-to-hip ratio, and skinfold measurements aim to capture this aspect but often fall short because of variation in techniques.

BMI does not account for muscle mass either, so fit athletes and bodybuilders can be classified as having obesity by BMI alone. More accurate body fat percent measures, such as dual-energy X-ray absorptiometry or MRI specifically for ectopic fat, are labor intensive, expensive, and not feasible to perform in a busy primary care or endocrinology clinic.
 

Assessing Risks From Obesity Beyond BMI

Clearly, better risk measures than BMI are needed, but until they are available, supplemental clinical tools can aid diagnosis and treatment decisions at obesity medicine specialty centers, endocrinology and diabetes centers, and those centers that focus on the treatment of obesity.

For example, a seca scale can measure percent body fat by bioelectric impedance analysis. This technique also has its limitations, but for persons who are well hydrated, it can be used as a baseline to determine efficacy of behavioral interventions, such as resistance-exercise training and a high-protein diet to protect muscle mass as the patient loses weight.

A lot also can be gleaned from diet and exercise history, social history, family history, and physical exam as well as laboratory analyses. For example, an Asian American patient with a BMI of 26 who has been gaining weight mostly in the abdominal region after age 35 years is likely to have cardiometabolic risk, and a family history can solidify that. An exam can show signs of acanthosis nigricans or an enlarged liver and generous abdominal adipose tissue. This would be the patient in whom you would want to obtain a hemoglobin A1c measurement in the chance that it is elevated at > 5.7 mg/dL, suggesting high risk for type 2 diabetes. 

A Fibrosis-4 score can assess the risk for liver disease from aspartate transaminase and alanine aminotransferase and platelet count and age, providing clues to cardiometabolic disease risk.

In the next 10, years there may be a better measure for cardiometabolic risk that is more accurate than BMI is. It could be the sagittal abdominal diameter, which has been purported to more accurately measure visceral abdominal fat. But this has not made it to be one of the vital signs in a busy primary care clinic, however. 
 

Will New Body Fat Tools Change Practice?

In the next 10 years, there may be an affordable gadget to scan the body to determine visceral vs subcutaneous deposition of fat — like radiography for tissue. Now, three-dimensional (3D) total-body scanners can obtain body composition, but they are extremely expensive. The more important clinical question is: How will the use of these imaging modalities change your practice protocol for a particular patient? 

Think about the FibroScan, a type of ultrasound used to determine fatty liver disease and fibrosis. We order the test for those patients in whom we already have a strong suspicion for liver disease and, in obesity practices, for fatty liver and metabolic-associated fatty liver disease or metabolic associated steatohepatitis.

The test results do much to educate the patient and help the patient understand the need for aggressive treatment for their obesity. But it doesn’t necessarily change the clinician’s practice protocols and decisions. We would still recommend weight management and medications or surgery to patients regardless of the findings. 

A FibroScan is an expense, and not all primary care or endocrine practitioners may feel it necessary to purchase one for the added benefit of patient education. And I would argue that a 3D body scanner is a great tool but more for educational purposes than to really determine practice decision-making or outcomes. 

In the meantime, an old-fashioned physical examination, along with a thorough medical, social, and family history should give even the busiest primary care provider enough information to decide whether their patient is a candidate for preventive measures to reduce body fat with diet, exercise, and medication as well as whether the patient is a candidate for metabolic bariatric surgery. Higher suspicion of cardiovascular risk at lower BMI ranges for various ethnicities can help primary care providers pick up on the patients with low BMI but who are at higher risk for type 2 diabetes or prediabetes and cardiovascular disease. 

So the answer to whether we need a better measure than the BMI: Yes, we do. We need a physical examination on all patients.

Dr. Apovian, professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, both in Boston, Massachusetts, disclosed ties with Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, L-Nutra, NeuroBo Pharm, Novo, OptumRx, Pain Script, Palatin, Pursuit by You, Roman Health, Xeno, and Riverview School.

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

Dry fasting, the practice of going without food and water, has enthusiastic advocates on TikTok, X, YouTube, and other social media platforms. Devotees claim a wide range of health effects, but medical professionals advise caution to ensure that the practice does more good than harm, especially for individuals with diabetes. 

Purported benefits and risks vary, depending on who is following the regimen and how long they abstain from food and water. Advocates on social media assert that dry fasting makes “intuition skyrocket” and puts autophagy on “overdrive.” Although such statements may rev up followers, there is little evidence to support these and many other dry-fasting claims. In fact, several physicians warned about unintended consequences.

“I had one patient who followed this fasting method often, and over time she developed kidney stones that led to a severe infection,” said Deena Adimoolam, MD, an endocrinologist in private practice in New York City and New Jersey. “Lack of both water and food can fuel hunger and increase the likelihood of overeating or binge eating once the fast is completed, which does not lead to weight loss. Untreated dehydration can lead to loss of consciousness.”

“For individuals with type 2 diabetes, dehydration can exacerbate hyperglycemia and increase the risk of complications such as diabetic ketoacidosis (DKA),” said Abeer Bader, lead clinical nutrition specialist at the Massachusetts General Hospital Weight Center in Boston. “Research also consistently shows that adequate hydration is crucial for maintaining physical and cognitive performance.”

Dry fasting also can lead to electrolyte imbalances, and the risk is higher for those with diabetes due to potential underlying kidney issues, Ms. Bader noted. “Prolonged dry fasting can result in nutrient deficiencies. For individuals with diabetes, maintaining adequate nutrition is crucial to manage blood sugar levels and overall health. The lack of both food and water can exacerbate deficiencies.”

Joanne Bruno, MD, an endocrinologist at NYU Langone Health, added, “Certain medications used for the management of type 2 diabetes, such as SGLT2 inhibitors, can cause dehydration. It is critical that patients stay well hydrated while on these medications to avoid serious side effects such as euglycemic DKA.”
 

What Exactly Is Dry Fasting?

Defining dry fasting, like any kind of fasting, has remained a challenge, according to authors of the first international consensus on fasting terminology, published on July 25 in Cell Metabolism. The clinical terminology “has remained heterogeneous and often confusing, with similar terms being used to define different fasting regimens ... reflecting the manifold contexts in which fasting is practiced.”

Indeed, dry fasting was among the most discussed terms by the consensus panel and went through several rounds before the panelists came to agreement. A few experts were critical of the practice, whereas those familiar with religious fasting traditions, such as during Ramadan, were clear about the importance of including this term in the consensus process.

“The dissent was resolved by the clarification that this form of fasting has historical and geographical extensions and that the present consensus process did not aim at evaluating therapeutic effectiveness or safety for any term defined,” the authors wrote.

The panel concluded that dry fasting is not the same as total or complete fasting because the latter can include water (such as water-only fasting). Their final definition of dry fasting is ‘’a fasting regimen during which a voluntary abstinence from all foods and beverages, including water, is practiced for a certain period of time.’’

Different types of fasting regimens, such as intermittent fasting, may include dry fasting, in which case it is referred to as “intermittent dry fasting.” This is defined in the consensus as intermittent fasting regimens that involve abstaining from food and fluid intake during the fasting interval, which typically lasts 9-20 hours. 

Most dry fasts, including religious ones, are maintained for a specific interval and are followed by a refeeding period. These fasts are not starvation, defined as no food or water intake for days.
 

What the Evidence Says

All that said, dry fasting by any other name remains dry fasting. “Abundant” evidence from animal studies suggests the potential of various types of fasting for disease prevention and treatment in humans, noted the authors of the consensus report, Along with the risks described above, small studies have explored short-term effects in people, all of which have yet to be established by larger and longer-term studies.

In a recent small study, researchers at Baylor College of Medicine, Houston, Texas, reported that dawn-to-dusk dry fasting for 30 days reduced levels of inflammatory cytokines in the 13 participants with a high body mass index. Earlier work by the group showed that dawn-to-dusk dry fasting for 30 days induced “anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome” in peripheral blood mononuclear cells of 14 individuals with metabolic syndrome (The researchers declined to comment for this article.)

Importantly, the health effects can vary among individuals for unknown reasons, found a recent cross-sectional study of fasting blood glucose (FBG) changes in 181 patients with type 2 diabetes during Ramadan intermittent fasting (RIF), which involves dry fasting during daylight hours for 1 month. The researchers classified participants into three groups: reduced average FBG levels (44%), no change in FBG levels (24%), and increased FBG levels (32%). The authors wrote that further studies are needed to identify factors associated with the differences and to identify “those who are great candidates for RIF.”

In contrast to some of the concerns expressed by clinicians, an exploratory study of daytime dry fasting among 34 healthy Baha’i volunteers in Germany concluded that the 19-day regimen “is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.” The authors acknowledge that a larger number and more diverse participants are needed to validate the findings and assess the impact on long-term health.
 

What to Advise Patients

For patients who want to fast as part of their weight loss regimen or to help manage diabetes, clinicians can consider suggesting “alternate ways of eating that might achieve similar goals,” Ms. Bader said. One is intermittent fasting without dry fasting: the 16:8 method (16 hours of fasting, 8 hours of eating) or the 5:2 method (normal eating for 5 days, reduced calorie intake for 2 days), which can support improved insulin sensitivity and metabolic health.

Caloric restriction can also work if the patient maintains a balanced diet that includes all essential nutrients, she said. A low-carbohydrate diet that focuses on limiting carbohydrate intake while increasing consumption of lean proteins and healthy fats has been shown to lower blood sugar levels and improve insulin sensitivity.

Other healthy strategies for patients include the Mediterranean diet, which emphasizes whole grains, fruits, vegetables, nuts, seeds, olive oil, and lean proteins such as fish, or a similar plant-based diet with less animal protein. Ms. Bader advises cultivating mindful eating, which involves paying attention to hunger and fullness cues, making thoughtful food choices, and focusing on being present during meals.

“Each of these dietary strategies offers potential benefits for managing type 2 diabetes and improving overall health,” Ms. Bader said. “I have not had any patients who have tried dry fasting specifically. However, I have encountered scenarios where individuals abstained from food and beverages due to religious practices. In those cases, we focused on ensuring that they maintained proper hydration and balanced nutrition during their eating periods to manage their diabetes effectively and prevent complications.”

Overall, Dr. Adimoolam suggests that clinicians help patients find a weight-loss plan that works best for them based on understanding the calories in the foods they like and don’t like. For fasting regimens, patients can be encouraged to choose one with fluids when possible, as well as intervals of time to fast and eat that work best for their lifestyle.

Ms. Bader, Dr. Bruno, and Dr. Adimoolam report no relevant conflicts.
 

A version of this article appeared on Medscape.com.

Dry fasting, the practice of going without food and water, has enthusiastic advocates on TikTok, X, YouTube, and other social media platforms. Devotees claim a wide range of health effects, but medical professionals advise caution to ensure that the practice does more good than harm, especially for individuals with diabetes. 

Purported benefits and risks vary, depending on who is following the regimen and how long they abstain from food and water. Advocates on social media assert that dry fasting makes “intuition skyrocket” and puts autophagy on “overdrive.” Although such statements may rev up followers, there is little evidence to support these and many other dry-fasting claims. In fact, several physicians warned about unintended consequences.

“I had one patient who followed this fasting method often, and over time she developed kidney stones that led to a severe infection,” said Deena Adimoolam, MD, an endocrinologist in private practice in New York City and New Jersey. “Lack of both water and food can fuel hunger and increase the likelihood of overeating or binge eating once the fast is completed, which does not lead to weight loss. Untreated dehydration can lead to loss of consciousness.”

“For individuals with type 2 diabetes, dehydration can exacerbate hyperglycemia and increase the risk of complications such as diabetic ketoacidosis (DKA),” said Abeer Bader, lead clinical nutrition specialist at the Massachusetts General Hospital Weight Center in Boston. “Research also consistently shows that adequate hydration is crucial for maintaining physical and cognitive performance.”

Dry fasting also can lead to electrolyte imbalances, and the risk is higher for those with diabetes due to potential underlying kidney issues, Ms. Bader noted. “Prolonged dry fasting can result in nutrient deficiencies. For individuals with diabetes, maintaining adequate nutrition is crucial to manage blood sugar levels and overall health. The lack of both food and water can exacerbate deficiencies.”

Joanne Bruno, MD, an endocrinologist at NYU Langone Health, added, “Certain medications used for the management of type 2 diabetes, such as SGLT2 inhibitors, can cause dehydration. It is critical that patients stay well hydrated while on these medications to avoid serious side effects such as euglycemic DKA.”
 

What Exactly Is Dry Fasting?

Defining dry fasting, like any kind of fasting, has remained a challenge, according to authors of the first international consensus on fasting terminology, published on July 25 in Cell Metabolism. The clinical terminology “has remained heterogeneous and often confusing, with similar terms being used to define different fasting regimens ... reflecting the manifold contexts in which fasting is practiced.”

Indeed, dry fasting was among the most discussed terms by the consensus panel and went through several rounds before the panelists came to agreement. A few experts were critical of the practice, whereas those familiar with religious fasting traditions, such as during Ramadan, were clear about the importance of including this term in the consensus process.

“The dissent was resolved by the clarification that this form of fasting has historical and geographical extensions and that the present consensus process did not aim at evaluating therapeutic effectiveness or safety for any term defined,” the authors wrote.

The panel concluded that dry fasting is not the same as total or complete fasting because the latter can include water (such as water-only fasting). Their final definition of dry fasting is ‘’a fasting regimen during which a voluntary abstinence from all foods and beverages, including water, is practiced for a certain period of time.’’

Different types of fasting regimens, such as intermittent fasting, may include dry fasting, in which case it is referred to as “intermittent dry fasting.” This is defined in the consensus as intermittent fasting regimens that involve abstaining from food and fluid intake during the fasting interval, which typically lasts 9-20 hours. 

Most dry fasts, including religious ones, are maintained for a specific interval and are followed by a refeeding period. These fasts are not starvation, defined as no food or water intake for days.
 

What the Evidence Says

All that said, dry fasting by any other name remains dry fasting. “Abundant” evidence from animal studies suggests the potential of various types of fasting for disease prevention and treatment in humans, noted the authors of the consensus report, Along with the risks described above, small studies have explored short-term effects in people, all of which have yet to be established by larger and longer-term studies.

In a recent small study, researchers at Baylor College of Medicine, Houston, Texas, reported that dawn-to-dusk dry fasting for 30 days reduced levels of inflammatory cytokines in the 13 participants with a high body mass index. Earlier work by the group showed that dawn-to-dusk dry fasting for 30 days induced “anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome” in peripheral blood mononuclear cells of 14 individuals with metabolic syndrome (The researchers declined to comment for this article.)

Importantly, the health effects can vary among individuals for unknown reasons, found a recent cross-sectional study of fasting blood glucose (FBG) changes in 181 patients with type 2 diabetes during Ramadan intermittent fasting (RIF), which involves dry fasting during daylight hours for 1 month. The researchers classified participants into three groups: reduced average FBG levels (44%), no change in FBG levels (24%), and increased FBG levels (32%). The authors wrote that further studies are needed to identify factors associated with the differences and to identify “those who are great candidates for RIF.”

In contrast to some of the concerns expressed by clinicians, an exploratory study of daytime dry fasting among 34 healthy Baha’i volunteers in Germany concluded that the 19-day regimen “is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.” The authors acknowledge that a larger number and more diverse participants are needed to validate the findings and assess the impact on long-term health.
 

What to Advise Patients

For patients who want to fast as part of their weight loss regimen or to help manage diabetes, clinicians can consider suggesting “alternate ways of eating that might achieve similar goals,” Ms. Bader said. One is intermittent fasting without dry fasting: the 16:8 method (16 hours of fasting, 8 hours of eating) or the 5:2 method (normal eating for 5 days, reduced calorie intake for 2 days), which can support improved insulin sensitivity and metabolic health.

Caloric restriction can also work if the patient maintains a balanced diet that includes all essential nutrients, she said. A low-carbohydrate diet that focuses on limiting carbohydrate intake while increasing consumption of lean proteins and healthy fats has been shown to lower blood sugar levels and improve insulin sensitivity.

Other healthy strategies for patients include the Mediterranean diet, which emphasizes whole grains, fruits, vegetables, nuts, seeds, olive oil, and lean proteins such as fish, or a similar plant-based diet with less animal protein. Ms. Bader advises cultivating mindful eating, which involves paying attention to hunger and fullness cues, making thoughtful food choices, and focusing on being present during meals.

“Each of these dietary strategies offers potential benefits for managing type 2 diabetes and improving overall health,” Ms. Bader said. “I have not had any patients who have tried dry fasting specifically. However, I have encountered scenarios where individuals abstained from food and beverages due to religious practices. In those cases, we focused on ensuring that they maintained proper hydration and balanced nutrition during their eating periods to manage their diabetes effectively and prevent complications.”

Overall, Dr. Adimoolam suggests that clinicians help patients find a weight-loss plan that works best for them based on understanding the calories in the foods they like and don’t like. For fasting regimens, patients can be encouraged to choose one with fluids when possible, as well as intervals of time to fast and eat that work best for their lifestyle.

Ms. Bader, Dr. Bruno, and Dr. Adimoolam report no relevant conflicts.
 

A version of this article appeared on Medscape.com.

Dry fasting, the practice of going without food and water, has enthusiastic advocates on TikTok, X, YouTube, and other social media platforms. Devotees claim a wide range of health effects, but medical professionals advise caution to ensure that the practice does more good than harm, especially for individuals with diabetes. 

Purported benefits and risks vary, depending on who is following the regimen and how long they abstain from food and water. Advocates on social media assert that dry fasting makes “intuition skyrocket” and puts autophagy on “overdrive.” Although such statements may rev up followers, there is little evidence to support these and many other dry-fasting claims. In fact, several physicians warned about unintended consequences.

“I had one patient who followed this fasting method often, and over time she developed kidney stones that led to a severe infection,” said Deena Adimoolam, MD, an endocrinologist in private practice in New York City and New Jersey. “Lack of both water and food can fuel hunger and increase the likelihood of overeating or binge eating once the fast is completed, which does not lead to weight loss. Untreated dehydration can lead to loss of consciousness.”

“For individuals with type 2 diabetes, dehydration can exacerbate hyperglycemia and increase the risk of complications such as diabetic ketoacidosis (DKA),” said Abeer Bader, lead clinical nutrition specialist at the Massachusetts General Hospital Weight Center in Boston. “Research also consistently shows that adequate hydration is crucial for maintaining physical and cognitive performance.”

Dry fasting also can lead to electrolyte imbalances, and the risk is higher for those with diabetes due to potential underlying kidney issues, Ms. Bader noted. “Prolonged dry fasting can result in nutrient deficiencies. For individuals with diabetes, maintaining adequate nutrition is crucial to manage blood sugar levels and overall health. The lack of both food and water can exacerbate deficiencies.”

Joanne Bruno, MD, an endocrinologist at NYU Langone Health, added, “Certain medications used for the management of type 2 diabetes, such as SGLT2 inhibitors, can cause dehydration. It is critical that patients stay well hydrated while on these medications to avoid serious side effects such as euglycemic DKA.”
 

What Exactly Is Dry Fasting?

Defining dry fasting, like any kind of fasting, has remained a challenge, according to authors of the first international consensus on fasting terminology, published on July 25 in Cell Metabolism. The clinical terminology “has remained heterogeneous and often confusing, with similar terms being used to define different fasting regimens ... reflecting the manifold contexts in which fasting is practiced.”

Indeed, dry fasting was among the most discussed terms by the consensus panel and went through several rounds before the panelists came to agreement. A few experts were critical of the practice, whereas those familiar with religious fasting traditions, such as during Ramadan, were clear about the importance of including this term in the consensus process.

“The dissent was resolved by the clarification that this form of fasting has historical and geographical extensions and that the present consensus process did not aim at evaluating therapeutic effectiveness or safety for any term defined,” the authors wrote.

The panel concluded that dry fasting is not the same as total or complete fasting because the latter can include water (such as water-only fasting). Their final definition of dry fasting is ‘’a fasting regimen during which a voluntary abstinence from all foods and beverages, including water, is practiced for a certain period of time.’’

Different types of fasting regimens, such as intermittent fasting, may include dry fasting, in which case it is referred to as “intermittent dry fasting.” This is defined in the consensus as intermittent fasting regimens that involve abstaining from food and fluid intake during the fasting interval, which typically lasts 9-20 hours. 

Most dry fasts, including religious ones, are maintained for a specific interval and are followed by a refeeding period. These fasts are not starvation, defined as no food or water intake for days.
 

What the Evidence Says

All that said, dry fasting by any other name remains dry fasting. “Abundant” evidence from animal studies suggests the potential of various types of fasting for disease prevention and treatment in humans, noted the authors of the consensus report, Along with the risks described above, small studies have explored short-term effects in people, all of which have yet to be established by larger and longer-term studies.

In a recent small study, researchers at Baylor College of Medicine, Houston, Texas, reported that dawn-to-dusk dry fasting for 30 days reduced levels of inflammatory cytokines in the 13 participants with a high body mass index. Earlier work by the group showed that dawn-to-dusk dry fasting for 30 days induced “anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome” in peripheral blood mononuclear cells of 14 individuals with metabolic syndrome (The researchers declined to comment for this article.)

Importantly, the health effects can vary among individuals for unknown reasons, found a recent cross-sectional study of fasting blood glucose (FBG) changes in 181 patients with type 2 diabetes during Ramadan intermittent fasting (RIF), which involves dry fasting during daylight hours for 1 month. The researchers classified participants into three groups: reduced average FBG levels (44%), no change in FBG levels (24%), and increased FBG levels (32%). The authors wrote that further studies are needed to identify factors associated with the differences and to identify “those who are great candidates for RIF.”

In contrast to some of the concerns expressed by clinicians, an exploratory study of daytime dry fasting among 34 healthy Baha’i volunteers in Germany concluded that the 19-day regimen “is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.” The authors acknowledge that a larger number and more diverse participants are needed to validate the findings and assess the impact on long-term health.
 

What to Advise Patients

For patients who want to fast as part of their weight loss regimen or to help manage diabetes, clinicians can consider suggesting “alternate ways of eating that might achieve similar goals,” Ms. Bader said. One is intermittent fasting without dry fasting: the 16:8 method (16 hours of fasting, 8 hours of eating) or the 5:2 method (normal eating for 5 days, reduced calorie intake for 2 days), which can support improved insulin sensitivity and metabolic health.

Caloric restriction can also work if the patient maintains a balanced diet that includes all essential nutrients, she said. A low-carbohydrate diet that focuses on limiting carbohydrate intake while increasing consumption of lean proteins and healthy fats has been shown to lower blood sugar levels and improve insulin sensitivity.

Other healthy strategies for patients include the Mediterranean diet, which emphasizes whole grains, fruits, vegetables, nuts, seeds, olive oil, and lean proteins such as fish, or a similar plant-based diet with less animal protein. Ms. Bader advises cultivating mindful eating, which involves paying attention to hunger and fullness cues, making thoughtful food choices, and focusing on being present during meals.

“Each of these dietary strategies offers potential benefits for managing type 2 diabetes and improving overall health,” Ms. Bader said. “I have not had any patients who have tried dry fasting specifically. However, I have encountered scenarios where individuals abstained from food and beverages due to religious practices. In those cases, we focused on ensuring that they maintained proper hydration and balanced nutrition during their eating periods to manage their diabetes effectively and prevent complications.”

Overall, Dr. Adimoolam suggests that clinicians help patients find a weight-loss plan that works best for them based on understanding the calories in the foods they like and don’t like. For fasting regimens, patients can be encouraged to choose one with fluids when possible, as well as intervals of time to fast and eat that work best for their lifestyle.

Ms. Bader, Dr. Bruno, and Dr. Adimoolam report no relevant conflicts.
 

A version of this article appeared on Medscape.com.

Consider this: If you’re taking your children to the beach, how do you protect them from drowning? You don’t tell them, “Don’t go into the ocean.” You teach them how to swim; you give them floaties; and you accompany them in the water and go in only when a lifeguard is present. In other words, you give them all the tools to protect themselves because you know they will go into the ocean anyway. 

Patients are diving into the ocean. Patients with obesity, who know that a treatment for their disease exists but is inaccessible, are diving into the ocean. Unfortunately, they are diving in without floaties or a lifeguard, and well-meaning bystanders are simply telling them to not go. 

Compounded peptides are an ocean of alternative therapies. Even though compounding pharmacists need specialized training, facilities and equipment need to be properly certified, and final dosage forms need extensive testing, pharmacies are not equal when it comes to sterile compounding. Regulatory agencies such as the US Food and Drug Administration (FDA) have expressed caution around compounded semaglutide. Professional societies such as the Obesity Medicine Association (OMA) advise against compounded peptides because they lack clinical trials that prove their safety and efficacy. Ask any individual doctor and you are likely to receive a range of opinions. 

As an endocrinologist specializing in obesity, I practice evidence-based medicine as much as possible. However, I also recognize how today’s dysfunctional medical system compels patients to dive into that ocean in search of an alternative solution. 

Doctors can’t be lifeguards, but we can at least empower patients who want to decide for themselves whether the risk of compounded peptides is worth it. 

With the help of pharmacists, compounding pharmacists, researchers, and clinicians, here is a checklist for patients who seek compounded semaglutide or tirzepatide: 

• Check the state licensing board website to see if there have been any complaints or disciplinary actions made against the pharmacy facility. These government-maintained websites vary in searchability and user-friendliness, but you are specifically looking for whether the FDA ever issued a 483 form.
• Ask for the pharmacy’s state board inspection report. There should be at least one of these reports, issued at the pharmacy’s founding, and there may be more depending on individual state regulations on frequencies of inspections.
• Ask if the compounding pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation is an extra optional step that some compounding pharmacies take to be legitimized by a third party.
• Ask if the pharmacy follows Current Good Manufacturing Practice (CGMP). CGMP is not required of 503a pharmacies, which are pharmacies that provide semaglutide or tirzepatide directly to patients, but following CGMP means an extra level of quality assurance. The bare minimum for anyone doing sterile compounding in the United States is to meet the standards found in the US Pharmacopeia, chapter <797>, Sterile Compounding.
• Ask your compounding pharmacy where they source the medication’s active pharmaceutical ingredient (API).
• Find out if this supplier is registered with the FDA by searching here or here.
• Confirm that semaglutide base, not semaglutide salt, is used in the compounding process.
• Request a certificate of analysis (COA) of the active pharmaceutical ingredient, which should be semaglutide base. This shows you whether the medication has impurities or byproducts due to its manufacturing process.
• Ask if they have third-party confirmation of potency, stability, and sterility testing of the final product.

In generating this guidance, I’m not endorsing compounded peptides, and in fact, I recognize that there is nothing keeping small-time compounding pharmacies from skirting some of these quality measures, falsifying records, and flying under the radar. However, I hope this checklist serves as a starting point for education and risk mitigation. If a compounder is unwilling or unable to answer these questions, consider it a red flag and look elsewhere. 

In an ideal world, the state regulators or the FDA would proactively supervise instead of reactively monitor; trusted compounding pharmacies would be systematically activated to ease medication shortages; and patients with obesity would have access to safe and efficacious treatments for their disease. Until then, we as providers can acknowledge the disappointments of our healthcare system while still developing realistic and individualized solutions that prioritize patient care and safety. 
 

Dr. Tchang is assistant professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, and a physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York. She is an adviser for Novo Nordisk, which manufactures Wegovy, and an adviser for Ro, a telehealth company that offers compounded semaglutide, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for Gelesis and Novo Nordisk.

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

Consider this: If you’re taking your children to the beach, how do you protect them from drowning? You don’t tell them, “Don’t go into the ocean.” You teach them how to swim; you give them floaties; and you accompany them in the water and go in only when a lifeguard is present. In other words, you give them all the tools to protect themselves because you know they will go into the ocean anyway. 

Patients are diving into the ocean. Patients with obesity, who know that a treatment for their disease exists but is inaccessible, are diving into the ocean. Unfortunately, they are diving in without floaties or a lifeguard, and well-meaning bystanders are simply telling them to not go. 

Compounded peptides are an ocean of alternative therapies. Even though compounding pharmacists need specialized training, facilities and equipment need to be properly certified, and final dosage forms need extensive testing, pharmacies are not equal when it comes to sterile compounding. Regulatory agencies such as the US Food and Drug Administration (FDA) have expressed caution around compounded semaglutide. Professional societies such as the Obesity Medicine Association (OMA) advise against compounded peptides because they lack clinical trials that prove their safety and efficacy. Ask any individual doctor and you are likely to receive a range of opinions. 

As an endocrinologist specializing in obesity, I practice evidence-based medicine as much as possible. However, I also recognize how today’s dysfunctional medical system compels patients to dive into that ocean in search of an alternative solution. 

Doctors can’t be lifeguards, but we can at least empower patients who want to decide for themselves whether the risk of compounded peptides is worth it. 

With the help of pharmacists, compounding pharmacists, researchers, and clinicians, here is a checklist for patients who seek compounded semaglutide or tirzepatide: 

• Check the state licensing board website to see if there have been any complaints or disciplinary actions made against the pharmacy facility. These government-maintained websites vary in searchability and user-friendliness, but you are specifically looking for whether the FDA ever issued a 483 form.
• Ask for the pharmacy’s state board inspection report. There should be at least one of these reports, issued at the pharmacy’s founding, and there may be more depending on individual state regulations on frequencies of inspections.
• Ask if the compounding pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation is an extra optional step that some compounding pharmacies take to be legitimized by a third party.
• Ask if the pharmacy follows Current Good Manufacturing Practice (CGMP). CGMP is not required of 503a pharmacies, which are pharmacies that provide semaglutide or tirzepatide directly to patients, but following CGMP means an extra level of quality assurance. The bare minimum for anyone doing sterile compounding in the United States is to meet the standards found in the US Pharmacopeia, chapter <797>, Sterile Compounding.
• Ask your compounding pharmacy where they source the medication’s active pharmaceutical ingredient (API).
• Find out if this supplier is registered with the FDA by searching here or here.
• Confirm that semaglutide base, not semaglutide salt, is used in the compounding process.
• Request a certificate of analysis (COA) of the active pharmaceutical ingredient, which should be semaglutide base. This shows you whether the medication has impurities or byproducts due to its manufacturing process.
• Ask if they have third-party confirmation of potency, stability, and sterility testing of the final product.

In generating this guidance, I’m not endorsing compounded peptides, and in fact, I recognize that there is nothing keeping small-time compounding pharmacies from skirting some of these quality measures, falsifying records, and flying under the radar. However, I hope this checklist serves as a starting point for education and risk mitigation. If a compounder is unwilling or unable to answer these questions, consider it a red flag and look elsewhere. 

In an ideal world, the state regulators or the FDA would proactively supervise instead of reactively monitor; trusted compounding pharmacies would be systematically activated to ease medication shortages; and patients with obesity would have access to safe and efficacious treatments for their disease. Until then, we as providers can acknowledge the disappointments of our healthcare system while still developing realistic and individualized solutions that prioritize patient care and safety. 
 

Dr. Tchang is assistant professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, and a physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York. She is an adviser for Novo Nordisk, which manufactures Wegovy, and an adviser for Ro, a telehealth company that offers compounded semaglutide, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for Gelesis and Novo Nordisk.

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

Consider this: If you’re taking your children to the beach, how do you protect them from drowning? You don’t tell them, “Don’t go into the ocean.” You teach them how to swim; you give them floaties; and you accompany them in the water and go in only when a lifeguard is present. In other words, you give them all the tools to protect themselves because you know they will go into the ocean anyway. 

Patients are diving into the ocean. Patients with obesity, who know that a treatment for their disease exists but is inaccessible, are diving into the ocean. Unfortunately, they are diving in without floaties or a lifeguard, and well-meaning bystanders are simply telling them to not go. 

Compounded peptides are an ocean of alternative therapies. Even though compounding pharmacists need specialized training, facilities and equipment need to be properly certified, and final dosage forms need extensive testing, pharmacies are not equal when it comes to sterile compounding. Regulatory agencies such as the US Food and Drug Administration (FDA) have expressed caution around compounded semaglutide. Professional societies such as the Obesity Medicine Association (OMA) advise against compounded peptides because they lack clinical trials that prove their safety and efficacy. Ask any individual doctor and you are likely to receive a range of opinions. 

As an endocrinologist specializing in obesity, I practice evidence-based medicine as much as possible. However, I also recognize how today’s dysfunctional medical system compels patients to dive into that ocean in search of an alternative solution. 

Doctors can’t be lifeguards, but we can at least empower patients who want to decide for themselves whether the risk of compounded peptides is worth it. 

With the help of pharmacists, compounding pharmacists, researchers, and clinicians, here is a checklist for patients who seek compounded semaglutide or tirzepatide: 

• Check the state licensing board website to see if there have been any complaints or disciplinary actions made against the pharmacy facility. These government-maintained websites vary in searchability and user-friendliness, but you are specifically looking for whether the FDA ever issued a 483 form.
• Ask for the pharmacy’s state board inspection report. There should be at least one of these reports, issued at the pharmacy’s founding, and there may be more depending on individual state regulations on frequencies of inspections.
• Ask if the compounding pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation is an extra optional step that some compounding pharmacies take to be legitimized by a third party.
• Ask if the pharmacy follows Current Good Manufacturing Practice (CGMP). CGMP is not required of 503a pharmacies, which are pharmacies that provide semaglutide or tirzepatide directly to patients, but following CGMP means an extra level of quality assurance. The bare minimum for anyone doing sterile compounding in the United States is to meet the standards found in the US Pharmacopeia, chapter <797>, Sterile Compounding.
• Ask your compounding pharmacy where they source the medication’s active pharmaceutical ingredient (API).
• Find out if this supplier is registered with the FDA by searching here or here.
• Confirm that semaglutide base, not semaglutide salt, is used in the compounding process.
• Request a certificate of analysis (COA) of the active pharmaceutical ingredient, which should be semaglutide base. This shows you whether the medication has impurities or byproducts due to its manufacturing process.
• Ask if they have third-party confirmation of potency, stability, and sterility testing of the final product.

In generating this guidance, I’m not endorsing compounded peptides, and in fact, I recognize that there is nothing keeping small-time compounding pharmacies from skirting some of these quality measures, falsifying records, and flying under the radar. However, I hope this checklist serves as a starting point for education and risk mitigation. If a compounder is unwilling or unable to answer these questions, consider it a red flag and look elsewhere. 

In an ideal world, the state regulators or the FDA would proactively supervise instead of reactively monitor; trusted compounding pharmacies would be systematically activated to ease medication shortages; and patients with obesity would have access to safe and efficacious treatments for their disease. Until then, we as providers can acknowledge the disappointments of our healthcare system while still developing realistic and individualized solutions that prioritize patient care and safety. 
 

Dr. Tchang is assistant professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, and a physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York. She is an adviser for Novo Nordisk, which manufactures Wegovy, and an adviser for Ro, a telehealth company that offers compounded semaglutide, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for Gelesis and Novo Nordisk.

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

Gary* is a 60-year-old race car driver with a history of insulin resistance, elevated cholesterol, and severe reflux. His wife sent him to me when his snoring became so loud and “violent” that she could no longer sleep in the same bedroom. 

She was desperate to help him lose weight in a sustained fashion. All his previous efforts were short-lived due to his self-described pizza and burger addiction. At 5 ft 9 in and 180 lb, his body mass index (BMI) was approximately 26.5 (normal is 18.5-24.9). 

On exam, his arms and legs were relatively thin, but he had a hard, protuberant belly. Given his body habits, comorbidities, and family history of early heart disease, I was worried that his weight would eventually become life-threatening. Solely on the basis of BMI criteria, however, he is not considered to be at high risk. 

This begs the question, are we relying too much on BMI and ignoring central adiposity (ie, belly fat) and comorbid conditions when identifying at-risk patients?

The European Association for the Study of Obesity (EASO) argues exactly this point in its new guidelines published in July 2024. Titled “A New Framework for the Diagnosis, Staging, and Management of Obesity in Adults,” the guidelines assert that obesity should be redefined as a chronic and relapsing adiposity-based disease which may start off as asymptomatic but often becomes life-threatening. 

The guidelines further argue that BMI does not appropriately predict cardiometabolic risk in patients with BMI < 35. Instead, in such patients we should incorporate the use of waist-to-height ratios to reflect the potentially deleterious presence of increased visceral fat. It expands the definition of high-risk patients to include those with BMI > 25 and a waist-to-height ratio > 0.5.

It also suggests that DEXA (dual-energy x-ray absorptiometry) or bioimpedance testing be used when BMI results are ambiguous. The European guidelines recommend considering screening more routinely for eating disorders (with psychometric testing) and depression. The guidelines highlight the importance of long-term goals and of physical activity, nutrition, and psychological support in addition to pharmaceutical treatments.

On the basis of these new guidelines, I attempted to start Gary on Wegovy (semaglutide) along with sending him to a health coach, dietitian, and trainer. Unfortunately, despite documenting a waist-to-height ratio of > 0.6 and elevated fat percentage of just over 30% using bioimpedance, my prior authorization and appeal were summarily rejected by his insurance provider. 

In the United States, pharmacotherapy is typically approved for patients with a BMI of 27 or higher with a comorbidity (like high blood pressure or elevated cholesterol levels) or a BMI over 30. This clearly highlights the need for updated criteria for weight loss medication. Thank goodness for compounded semaglutide to fill this void until the medical world catches up with the EASO guidelines. 

Now on compounded semaglutide, Gary has lost 15 lb. His once rounded belly is nearly flat, and he has a normal waist-to-height ratio. While his dietary choices still leave something to be desired, his portion sizes are much smaller. His snoring has improved considerably. His most recent bioimpedance testing showed a reduced fat percentage of just under 25%.

*Patient’s name has been changed 

Caroline Messer, MD, is Clinical Assistant Professor, Mount Sinai School of Medicine, and Associate Professor, Hofstra School of Medicine, both in New York. She has disclosed no relevant financial relationships.

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

Gary* is a 60-year-old race car driver with a history of insulin resistance, elevated cholesterol, and severe reflux. His wife sent him to me when his snoring became so loud and “violent” that she could no longer sleep in the same bedroom. 

She was desperate to help him lose weight in a sustained fashion. All his previous efforts were short-lived due to his self-described pizza and burger addiction. At 5 ft 9 in and 180 lb, his body mass index (BMI) was approximately 26.5 (normal is 18.5-24.9). 

On exam, his arms and legs were relatively thin, but he had a hard, protuberant belly. Given his body habits, comorbidities, and family history of early heart disease, I was worried that his weight would eventually become life-threatening. Solely on the basis of BMI criteria, however, he is not considered to be at high risk. 

This begs the question, are we relying too much on BMI and ignoring central adiposity (ie, belly fat) and comorbid conditions when identifying at-risk patients?

The European Association for the Study of Obesity (EASO) argues exactly this point in its new guidelines published in July 2024. Titled “A New Framework for the Diagnosis, Staging, and Management of Obesity in Adults,” the guidelines assert that obesity should be redefined as a chronic and relapsing adiposity-based disease which may start off as asymptomatic but often becomes life-threatening. 

The guidelines further argue that BMI does not appropriately predict cardiometabolic risk in patients with BMI < 35. Instead, in such patients we should incorporate the use of waist-to-height ratios to reflect the potentially deleterious presence of increased visceral fat. It expands the definition of high-risk patients to include those with BMI > 25 and a waist-to-height ratio > 0.5.

It also suggests that DEXA (dual-energy x-ray absorptiometry) or bioimpedance testing be used when BMI results are ambiguous. The European guidelines recommend considering screening more routinely for eating disorders (with psychometric testing) and depression. The guidelines highlight the importance of long-term goals and of physical activity, nutrition, and psychological support in addition to pharmaceutical treatments.

On the basis of these new guidelines, I attempted to start Gary on Wegovy (semaglutide) along with sending him to a health coach, dietitian, and trainer. Unfortunately, despite documenting a waist-to-height ratio of > 0.6 and elevated fat percentage of just over 30% using bioimpedance, my prior authorization and appeal were summarily rejected by his insurance provider. 

In the United States, pharmacotherapy is typically approved for patients with a BMI of 27 or higher with a comorbidity (like high blood pressure or elevated cholesterol levels) or a BMI over 30. This clearly highlights the need for updated criteria for weight loss medication. Thank goodness for compounded semaglutide to fill this void until the medical world catches up with the EASO guidelines. 

Now on compounded semaglutide, Gary has lost 15 lb. His once rounded belly is nearly flat, and he has a normal waist-to-height ratio. While his dietary choices still leave something to be desired, his portion sizes are much smaller. His snoring has improved considerably. His most recent bioimpedance testing showed a reduced fat percentage of just under 25%.

*Patient’s name has been changed 

Caroline Messer, MD, is Clinical Assistant Professor, Mount Sinai School of Medicine, and Associate Professor, Hofstra School of Medicine, both in New York. She has disclosed no relevant financial relationships.

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

Gary* is a 60-year-old race car driver with a history of insulin resistance, elevated cholesterol, and severe reflux. His wife sent him to me when his snoring became so loud and “violent” that she could no longer sleep in the same bedroom. 

She was desperate to help him lose weight in a sustained fashion. All his previous efforts were short-lived due to his self-described pizza and burger addiction. At 5 ft 9 in and 180 lb, his body mass index (BMI) was approximately 26.5 (normal is 18.5-24.9). 

On exam, his arms and legs were relatively thin, but he had a hard, protuberant belly. Given his body habits, comorbidities, and family history of early heart disease, I was worried that his weight would eventually become life-threatening. Solely on the basis of BMI criteria, however, he is not considered to be at high risk. 

This begs the question, are we relying too much on BMI and ignoring central adiposity (ie, belly fat) and comorbid conditions when identifying at-risk patients?

The European Association for the Study of Obesity (EASO) argues exactly this point in its new guidelines published in July 2024. Titled “A New Framework for the Diagnosis, Staging, and Management of Obesity in Adults,” the guidelines assert that obesity should be redefined as a chronic and relapsing adiposity-based disease which may start off as asymptomatic but often becomes life-threatening. 

The guidelines further argue that BMI does not appropriately predict cardiometabolic risk in patients with BMI < 35. Instead, in such patients we should incorporate the use of waist-to-height ratios to reflect the potentially deleterious presence of increased visceral fat. It expands the definition of high-risk patients to include those with BMI > 25 and a waist-to-height ratio > 0.5.

It also suggests that DEXA (dual-energy x-ray absorptiometry) or bioimpedance testing be used when BMI results are ambiguous. The European guidelines recommend considering screening more routinely for eating disorders (with psychometric testing) and depression. The guidelines highlight the importance of long-term goals and of physical activity, nutrition, and psychological support in addition to pharmaceutical treatments.

On the basis of these new guidelines, I attempted to start Gary on Wegovy (semaglutide) along with sending him to a health coach, dietitian, and trainer. Unfortunately, despite documenting a waist-to-height ratio of > 0.6 and elevated fat percentage of just over 30% using bioimpedance, my prior authorization and appeal were summarily rejected by his insurance provider. 

In the United States, pharmacotherapy is typically approved for patients with a BMI of 27 or higher with a comorbidity (like high blood pressure or elevated cholesterol levels) or a BMI over 30. This clearly highlights the need for updated criteria for weight loss medication. Thank goodness for compounded semaglutide to fill this void until the medical world catches up with the EASO guidelines. 

Now on compounded semaglutide, Gary has lost 15 lb. His once rounded belly is nearly flat, and he has a normal waist-to-height ratio. While his dietary choices still leave something to be desired, his portion sizes are much smaller. His snoring has improved considerably. His most recent bioimpedance testing showed a reduced fat percentage of just under 25%.

*Patient’s name has been changed 

Caroline Messer, MD, is Clinical Assistant Professor, Mount Sinai School of Medicine, and Associate Professor, Hofstra School of Medicine, both in New York. She has disclosed no relevant financial relationships.

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

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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