Clinical Endocrinology News

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.

1. Public health officials will prioritize dietary quality over quantity.

Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.

2. Antiobesity medications will target fat loss instead of weight loss.

Currently, the US Food and Drug Administration requires antiobesity medications to prove safe weight loss of ≥ 5% over placebo. The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.

3. Increasing energy expenditure is the holy grail of obesity research.

The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).

4. Chronic disease without chronic medications.

Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.

5. Barriers to access are barriers to progress.

The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.

Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.

Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”

The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.

I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.

1. Public health officials will prioritize dietary quality over quantity.

Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.

2. Antiobesity medications will target fat loss instead of weight loss.

Currently, the US Food and Drug Administration requires antiobesity medications to prove safe weight loss of ≥ 5% over placebo. The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.

3. Increasing energy expenditure is the holy grail of obesity research.

The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).

4. Chronic disease without chronic medications.

Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.

5. Barriers to access are barriers to progress.

The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.

Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.

Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”

The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.

I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

As more and more treatments for obesity become available, what does the future hold for these patients? Here are five things that clinicians need to know.

1. Public health officials will prioritize dietary quality over quantity.

Dietitians, healthcare providers, and scientists are already prioritizing the quality of calories, and now policymakers are aligning with this goal, with calls for more research on ultraprocessed foods (UPFs) to answer the key question, “Why do UPFs cause people to eat 500 more calories per day compared with unprocessed foods?” The food industry has taken notice of the potential “Ozempic effect” associated with reduced spending on groceries and is responding with product lines “designed to complement” glucagon-like peptide-1 receptor agonists (GLP-1 RAs) while simultaneously lobbying against any UPF reform. However, with emerging data on how sugar taxes may reduce sales and Congress honing in on the diabetes epidemic, we are hopeful that change is coming in 2024.

2. Antiobesity medications will target fat loss instead of weight loss.

Currently, the US Food and Drug Administration requires antiobesity medications to prove safe weight loss of ≥ 5% over placebo. The focus on weight has been long-standing, but with highly effective medications like tirzepatide causing about 20% weight loss, attention is shifting to body composition — namely, how do we optimize fat loss while preserving muscle? We are seeing this transition in the research community. Bimagrumab, for example, a once-monthly injection that increases muscle mass and decreases fat mass, is being tested in a phase 3 clinical trial alongside semaglutide. Agents initially designed for spinal muscular atrophy, like apitegromab and taldefgrobep alfa, are being repurposed for obesity. Watch for results of these phase 2 trials in 2024.

3. Increasing energy expenditure is the holy grail of obesity research.

The success of GLP-1 RAs, and the even greater success of dual- and triple-target agents like tirzepatide and retatrutide, tells us that obesity is, indeed, a hormone problem. These medications primarily cause weight loss by suppressing appetite and reducing caloric intake. As scientists develop more therapeutics to normalize appetite regulation, attention will shift to optimizing energy expenditure. Researchers are already investigating brown fat, mitochondrial uncouplers, and skeletal muscle metabolism, but no agent thus far has been proven to be both safe and effective in increasing energy expenditure. Of these, keep an eye on clinical trials involving brown fat and the excitement over the anti-inflammatory cytokine growth differentiating factor 15 (GDF15).

4. Chronic disease without chronic medications.

Obesity is a chronic disease, just like hypertension or diabetes. Similarly, medications that treat chronic diseases are expected to be taken long-term because discontinuation often results in disease recurrence. However, obesity research is getting closer and closer to options that require less frequent administration. Bimagrumab, for example, is a once-monthly injection. In endocrinology, the premier example is osteoporosis: Osteoporosis can be treated with just 3 years of an annual injection and never require treatment again. In obesity, anticipate more basic science discoveries aimed at developing safe and specific treatments that are truly disease-modifying — ones that reverse appetitive dysregulation, reduce proinflammatory adiposity, and optimize anabolic metabolism.

5. Barriers to access are barriers to progress.

The biggest challenge to obesity treatment today is access: drug shortages, medication costs, and lack of obesity medicine providers. Shortages of medications like semaglutide 2.4 mg are being driven by high “demand”; in other words, manufacturers failed to anticipate the massive interest in antiobesity medications.

Medicare and most state Medicaid programs don’t cover these medications; commercial payers are refusing, reversing, or limiting coverage. An out-of-pocket monthly cost over $1000 limits affordability for the majority of Americans.

Seeking care from an obesity medicine doctor is a challenge as well. Over 40% of US adults have obesity, but less than 1% of doctors are certified in obesity medicine. Meanwhile, private equity is eager to address the lack of access through compounding pharmacies, medispas, or telemedicine services, but the quality of care varies greatly. Some companies purposely avoid the term “patient,” preferring ethics-free labels like “consumers” or “members.”

The $100 billion–dollar weight loss industry unfortunately has created financial incentives that drive obesity commerce over obesity care. Because of these barriers, the epidemic of obesity, with a prevalence projected to be 50% by 2030, will not be solved or slowed despite the scientific progress in obesity treatment. A single silver lining exists among policymakers who are aiming to correct our costly sick-care system in steps, starting with pharmacy benefit manager reform. Five of these bills are the ones to track in 2024: Pharmacy Benefit Manager Reform Act, Pharmacy Benefits Manager Accountability Act, Pharmacy Benefit Manager Sunshine and Accountability Act, Pharmacy Benefit Manager Transparency Act of 2023, and Lower Costs, More Transparency Act.

I believe that these five things will have the most impact on the treatment of our patients with obesity. Stay tuned throughout the year as I share updates in obesity research, pharmacotherapy, and public policy.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — A combination of oral antihyperglycemics was as effective as insulin for managing gestational diabetes, based on data from more than 800 individuals.

After diet control, both insulin and oral agents such as metformin and glibenclamide are used as a first-line treatment for gestational diabetes mellitus, Doortje Rademaker, MD, of Amsterdam University Medical Center, the Netherlands, said in a presentation at the Pregnancy Meeting (abstract 28).

Oral antihyperglycemic agents (OAAs) are thought to be comparable to insulin in preventing large-for-gestational-age (LGA) infants at birth and potentially more convenient for patients, Dr. Rademaker said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Metformin and glibenclamide monotherapy as first-line treatment for gestational diabetes (GDM) are often used as patient-friendly alternatives to insulin. However, side effects are a concern, and data on the use of sequential and combined metformin and glibenclamide compared with insulin are lacking, she said.

In the study known as the SUGAR-DIP trial, Dr. Rademaker and colleagues recruited 821 women older than 18 years with singleton pregnancies between 16 weeks’ and 34 weeks’ gestation who had insufficient glycemic control with diet alone.

The study was conducted between 2016 and 2022; 409 women were randomized to OAAs and 412 to insulin. The mean age of the participants was 33 years, and 58% were White.

The OAA group received metformin initially, with the addition of up to 15 mg/day of glibenclamide in cases of insufficient glycemic control. Those who still experienced insufficient glycemic control were given insulin. The insulin group received injections according to usual standard of care.

The primary outcome was neonatal LGA, defined as birth weight above the 90th percentile. Secondary outcomes included patient satisfaction based on the Diabetes Treatment Satisfaction Questionnaire.

The intent-to-treat population included 406 women in the OAA group and 398 in the insulin group.

Overall, LGA rates were 23.9% in the OAA group vs. 19.9% in the insulin group. The absolute risk difference was 4%, with P values of .09 for noninferiority and .17 for superiority, Dr. Rademaker said in her presentation.

Notably, the OAA treatment led to lower maternal weight gain, although side effects were similar between the groups, she said. Neonates in the OAA group were significantly more likely to need intravenous glucose therapy (6.4% vs. 3.2%, P = .04). However, gestational weight gain was significantly lower in the OAA group than the insulin group (mean of 9.3 kg vs. 10.4 kg, P = .03).

Rates of maternal hypoglycemia were higher in the OAA group (21% vs. 11%), and 20% of women in the OAA group needed insulin therapy.

Serious adverse events were similar between the groups, but more side effects overall were reported in the OAA group than in the insulin group (77.9% vs. 55.9%, P < .001). The most common patient-reported side effects in the OAA group were nausea and diarrhea (nearly 40% for each), while headache and fatigue were the most common side effects in the insulin group.

Participants in both groups reported high levels of treatment satisfaction, with median scores of 5 on a scale of 0-6, Dr. Rademaker said. However, the data supported the researchers’ hypothesis of greater satisfaction with oral therapy. Patients in the OAA group were more likely to recommend their treatment to others than were those in the insulin group, with ratings of 5 vs. 4 on a scale of 0-6, and significantly more women in the OAA group said they would be inclined to continue their current treatment (5 vs. 4, P < .001 for both).

Study limitations included the open-label design. However, the results support the use of oral treatments as a noninferior alternative to insulin for preventing LGA in women with gestational diabetes, Dr. Rademaker said.
 

Data Support Orals as Effective Gestational Diabetes Option

“Treatment of gestational diabetes is important for optimal pregnancy outcomes,” Catherine Spong, MD, a maternal-fetal medicine specialist at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

Although the American College of Obstetrics and Gynecology recommends insulin as the first-line therapy for gestational diabetes, many individuals opt for OAAs for the ease of an oral medication compared with injections, she said.

The current study authors evaluated whether OAAs were noninferior to insulin alone. “The size of oral [antihyperglycemic] agents suggests they can cross the placenta and may result in hypoglycemia in the fetus,” she said.

Although the overall LGA rate in the current study seems high, the rate of LGA is increased in diabetes generally, she added.

A key takeaway was that although individuals who used oral agents were more likely to recommend their treatment and to continue their therapy, 20% of these patients needed insulin therapy, Dr. Spong said.

Additional research is needed to explore the effect of gestational diabetes treatments on the fetus, Dr. Spong said in an interview. Research questions include whether hypoglycemia is more common in women who received oral agents, whether the agents crossed the placenta, and long-term effects, she said.

The study was supported by a grant from the Dutch Organization for Health Research and Development. Dr. Rademaker had no financial conflicts to disclose. One of the study coauthors disclosed serving as a consultant for ObsEva and Merck, and travel support from Merck, as well as support from the National Health and Medical Research Council. Dr. Spong had no financial conflicts to disclose.

TOPLINE:

Despite diabetes technology, many with type 1 diabetes (T1D) miss glycemic targets and experience severe hypoglycemia and impaired awareness of hypoglycemia (IAH). 

METHODOLOGY:

• The clinical management of T1D through technology is now recognized as the standard of care, but its real-world impact on glycemic targets and severe hypoglycemic events and IAH is unclear.
• Researchers assessed the self-reported prevalence of glycemic metrics, severe hypoglycemia, and hypoglycemia awareness according to the use of continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems.
• They enrolled 2044 individuals diagnosed with T1D for at least 2 years (mean age, 43.0 years; 72.1% women; 95.4% White) from the T1D Exchange Registry and online communities who filled an online survey.
• Participants were stratified on the basis of the presence or absence of CGM and different insulin delivery methods (multiple daily injections, conventional pumps, or AID systems).
• The primary outcome was the proportion of participants who achieved glycemic targets (self-reported A1c), had severe hypoglycemia (any low glucose incidence in 12 months), and/or IAH (a modified Gold score on a seven-point Likert scale).

TAKEAWAY:

• Most participants (91.7%) used CGM, and 50.8% of CGM users used an AID system.
• Despite advanced interventions, only 59.6% (95% CI, 57.3%-61.8%) of CGM users met the glycemic target (A1c < 7%), while nearly 40% of CGM users and 35.6% of AID users didn’t reach the target.
• At least one event of severe hypoglycemia in the previous 12 months was reported in 10.8% of CGM users and 16.6% of those using an AID system.
• IAH prevalence was seen in 31.1% (95% CI, 29.0%-33.2%) and 30.3% (95% CI, 17.5%-33.3%) of participants using CGM and CGM + AID, respectively.

IN PRACTICE:

“Educational initiatives continue to be important for all individuals with type 1 diabetes, and the development of novel therapeutic options and strategies, including bihormonal AID systems and beta-cell replacement, will be required to enable more of these individuals to meet treatment goals,” the authors wrote.

SOURCE:

The study, published online in Diabetes Care, was led by Jennifer L. Sherr, MD, PhD, Yale School of Medicine, New Haven, Connecticut.

LIMITATIONS:

The survey participants in this study were from the T1D Exchange online community, who tend to be highly involved, have technology experience, and are more likely to achieve glycemic targets. The data reported as part of the survey were based on self-reports by participants and may be subject to recall bias. Notably, severe hypoglycemic events may be overreported by individuals using CGM and AID systems due to sensor alarms.

DISCLOSURES:

The study was funded by Vertex Pharmaceuticals. Several authors disclosed financial relationships, including grants, consulting fees, honoraria, stock ownership, and employment with pharmaceutical and device companies and other entities.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite diabetes technology, many with type 1 diabetes (T1D) miss glycemic targets and experience severe hypoglycemia and impaired awareness of hypoglycemia (IAH). 

METHODOLOGY:

• The clinical management of T1D through technology is now recognized as the standard of care, but its real-world impact on glycemic targets and severe hypoglycemic events and IAH is unclear.
• Researchers assessed the self-reported prevalence of glycemic metrics, severe hypoglycemia, and hypoglycemia awareness according to the use of continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems.
• They enrolled 2044 individuals diagnosed with T1D for at least 2 years (mean age, 43.0 years; 72.1% women; 95.4% White) from the T1D Exchange Registry and online communities who filled an online survey.
• Participants were stratified on the basis of the presence or absence of CGM and different insulin delivery methods (multiple daily injections, conventional pumps, or AID systems).
• The primary outcome was the proportion of participants who achieved glycemic targets (self-reported A1c), had severe hypoglycemia (any low glucose incidence in 12 months), and/or IAH (a modified Gold score on a seven-point Likert scale).

TAKEAWAY:

• Most participants (91.7%) used CGM, and 50.8% of CGM users used an AID system.
• Despite advanced interventions, only 59.6% (95% CI, 57.3%-61.8%) of CGM users met the glycemic target (A1c < 7%), while nearly 40% of CGM users and 35.6% of AID users didn’t reach the target.
• At least one event of severe hypoglycemia in the previous 12 months was reported in 10.8% of CGM users and 16.6% of those using an AID system.
• IAH prevalence was seen in 31.1% (95% CI, 29.0%-33.2%) and 30.3% (95% CI, 17.5%-33.3%) of participants using CGM and CGM + AID, respectively.

IN PRACTICE:

“Educational initiatives continue to be important for all individuals with type 1 diabetes, and the development of novel therapeutic options and strategies, including bihormonal AID systems and beta-cell replacement, will be required to enable more of these individuals to meet treatment goals,” the authors wrote.

SOURCE:

The study, published online in Diabetes Care, was led by Jennifer L. Sherr, MD, PhD, Yale School of Medicine, New Haven, Connecticut.

LIMITATIONS:

The survey participants in this study were from the T1D Exchange online community, who tend to be highly involved, have technology experience, and are more likely to achieve glycemic targets. The data reported as part of the survey were based on self-reports by participants and may be subject to recall bias. Notably, severe hypoglycemic events may be overreported by individuals using CGM and AID systems due to sensor alarms.

DISCLOSURES:

The study was funded by Vertex Pharmaceuticals. Several authors disclosed financial relationships, including grants, consulting fees, honoraria, stock ownership, and employment with pharmaceutical and device companies and other entities.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite diabetes technology, many with type 1 diabetes (T1D) miss glycemic targets and experience severe hypoglycemia and impaired awareness of hypoglycemia (IAH). 

METHODOLOGY:

• The clinical management of T1D through technology is now recognized as the standard of care, but its real-world impact on glycemic targets and severe hypoglycemic events and IAH is unclear.
• Researchers assessed the self-reported prevalence of glycemic metrics, severe hypoglycemia, and hypoglycemia awareness according to the use of continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems.
• They enrolled 2044 individuals diagnosed with T1D for at least 2 years (mean age, 43.0 years; 72.1% women; 95.4% White) from the T1D Exchange Registry and online communities who filled an online survey.
• Participants were stratified on the basis of the presence or absence of CGM and different insulin delivery methods (multiple daily injections, conventional pumps, or AID systems).
• The primary outcome was the proportion of participants who achieved glycemic targets (self-reported A1c), had severe hypoglycemia (any low glucose incidence in 12 months), and/or IAH (a modified Gold score on a seven-point Likert scale).

TAKEAWAY:

• Most participants (91.7%) used CGM, and 50.8% of CGM users used an AID system.
• Despite advanced interventions, only 59.6% (95% CI, 57.3%-61.8%) of CGM users met the glycemic target (A1c < 7%), while nearly 40% of CGM users and 35.6% of AID users didn’t reach the target.
• At least one event of severe hypoglycemia in the previous 12 months was reported in 10.8% of CGM users and 16.6% of those using an AID system.
• IAH prevalence was seen in 31.1% (95% CI, 29.0%-33.2%) and 30.3% (95% CI, 17.5%-33.3%) of participants using CGM and CGM + AID, respectively.

IN PRACTICE:

“Educational initiatives continue to be important for all individuals with type 1 diabetes, and the development of novel therapeutic options and strategies, including bihormonal AID systems and beta-cell replacement, will be required to enable more of these individuals to meet treatment goals,” the authors wrote.

SOURCE:

The study, published online in Diabetes Care, was led by Jennifer L. Sherr, MD, PhD, Yale School of Medicine, New Haven, Connecticut.

LIMITATIONS:

The survey participants in this study were from the T1D Exchange online community, who tend to be highly involved, have technology experience, and are more likely to achieve glycemic targets. The data reported as part of the survey were based on self-reports by participants and may be subject to recall bias. Notably, severe hypoglycemic events may be overreported by individuals using CGM and AID systems due to sensor alarms.

DISCLOSURES:

The study was funded by Vertex Pharmaceuticals. Several authors disclosed financial relationships, including grants, consulting fees, honoraria, stock ownership, and employment with pharmaceutical and device companies and other entities.

A version of this article appeared on Medscape.com.

TOPLINE:

Oral intragastric expandable capsules taken twice daily before meals reduce body weight in adults with overweight or obesity compared with placebo, with mild gastrointestinal adverse events.

METHODOLOGY:

• Numerous anti-obesity pharmacotherapies have demonstrated effectiveness in reducing weight, but they may lead to side effects.
• This 24-week phase 3 randomized placebo-controlled study evaluated 2.24 g oral intragastric expandable capsules for weight loss in 280 adults (ages 18-60 years) with overweight or obesity (body mass index ≥ 24 kg/m2).
• One capsule, taken before lunch and dinner with water, expands to fill about one quarter of average stomach volume and then passes through the body, similar to the US Food and Drug Administration–cleared device Plenity.
• Primary endpoints were the percentage change in body weight from baseline and the weight loss response rate (weight loss of at least 5% of baseline body weight) at week 24.
• Researchers analyzed efficacy outcomes in two ways: Intention to treat (a full analysis based on groups to which they were randomly assigned) and per protocol (based on data from participants who follow the protocol).

TAKEAWAY:

• At 24 weeks, the change in mean body weight was higher with intragastric expandable capsules than with placebo using the per protocol set (estimated treatment difference [ETD], −3.6%; P < .001), with similar results using the full analysis set.
• The weight loss response rate at 24 weeks was higher with intragastric expandable capsules than with placebo using the per protocol set (ETD, 29.6%; P < .001), with similar results using the full analysis set.
• Reduction in fasting insulin levels was higher with intragastric expandable capsules than with placebo (P = .008), while improvements in the lipid profile, fasting plasma glucose levels, and heart rate were similar between the groups.
• Gastrointestinal disorders were reported in 25.0% of participants in the intragastric expandable capsule group compared with 21.9% in the placebo group, with most being transient and mild in severity.

IN PRACTICE:

“As a mild and safe anti-obesity medication, intragastric expandable capsules provide a new therapeutic choice for individuals with overweight or obesity, helping them to enhance and maintain the effect of diet restriction,” wrote the authors.

SOURCE:

Difei Lu, MD, Department of Endocrinology, Peking University First Hospital, Beijing, China, led the study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study included individuals who were overweight or obese, who might have been more willing to lose weight than the general population. Moreover, only 3.25% of the participants had type 2 diabetes, and participants were relatively young. This may have reduced the potential to discover metabolic or cardiovascular improvement by the product.

DISCLOSURES:

This study was funded by Xiamen Junde Pharmaceutical Technology. The authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Oral intragastric expandable capsules taken twice daily before meals reduce body weight in adults with overweight or obesity compared with placebo, with mild gastrointestinal adverse events.

METHODOLOGY:

• Numerous anti-obesity pharmacotherapies have demonstrated effectiveness in reducing weight, but they may lead to side effects.
• This 24-week phase 3 randomized placebo-controlled study evaluated 2.24 g oral intragastric expandable capsules for weight loss in 280 adults (ages 18-60 years) with overweight or obesity (body mass index ≥ 24 kg/m2).
• One capsule, taken before lunch and dinner with water, expands to fill about one quarter of average stomach volume and then passes through the body, similar to the US Food and Drug Administration–cleared device Plenity.
• Primary endpoints were the percentage change in body weight from baseline and the weight loss response rate (weight loss of at least 5% of baseline body weight) at week 24.
• Researchers analyzed efficacy outcomes in two ways: Intention to treat (a full analysis based on groups to which they were randomly assigned) and per protocol (based on data from participants who follow the protocol).

TAKEAWAY:

• At 24 weeks, the change in mean body weight was higher with intragastric expandable capsules than with placebo using the per protocol set (estimated treatment difference [ETD], −3.6%; P < .001), with similar results using the full analysis set.
• The weight loss response rate at 24 weeks was higher with intragastric expandable capsules than with placebo using the per protocol set (ETD, 29.6%; P < .001), with similar results using the full analysis set.
• Reduction in fasting insulin levels was higher with intragastric expandable capsules than with placebo (P = .008), while improvements in the lipid profile, fasting plasma glucose levels, and heart rate were similar between the groups.
• Gastrointestinal disorders were reported in 25.0% of participants in the intragastric expandable capsule group compared with 21.9% in the placebo group, with most being transient and mild in severity.

IN PRACTICE:

“As a mild and safe anti-obesity medication, intragastric expandable capsules provide a new therapeutic choice for individuals with overweight or obesity, helping them to enhance and maintain the effect of diet restriction,” wrote the authors.

SOURCE:

Difei Lu, MD, Department of Endocrinology, Peking University First Hospital, Beijing, China, led the study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study included individuals who were overweight or obese, who might have been more willing to lose weight than the general population. Moreover, only 3.25% of the participants had type 2 diabetes, and participants were relatively young. This may have reduced the potential to discover metabolic or cardiovascular improvement by the product.

DISCLOSURES:

This study was funded by Xiamen Junde Pharmaceutical Technology. The authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Oral intragastric expandable capsules taken twice daily before meals reduce body weight in adults with overweight or obesity compared with placebo, with mild gastrointestinal adverse events.

METHODOLOGY:

• Numerous anti-obesity pharmacotherapies have demonstrated effectiveness in reducing weight, but they may lead to side effects.
• This 24-week phase 3 randomized placebo-controlled study evaluated 2.24 g oral intragastric expandable capsules for weight loss in 280 adults (ages 18-60 years) with overweight or obesity (body mass index ≥ 24 kg/m2).
• One capsule, taken before lunch and dinner with water, expands to fill about one quarter of average stomach volume and then passes through the body, similar to the US Food and Drug Administration–cleared device Plenity.
• Primary endpoints were the percentage change in body weight from baseline and the weight loss response rate (weight loss of at least 5% of baseline body weight) at week 24.
• Researchers analyzed efficacy outcomes in two ways: Intention to treat (a full analysis based on groups to which they were randomly assigned) and per protocol (based on data from participants who follow the protocol).

TAKEAWAY:

• At 24 weeks, the change in mean body weight was higher with intragastric expandable capsules than with placebo using the per protocol set (estimated treatment difference [ETD], −3.6%; P < .001), with similar results using the full analysis set.
• The weight loss response rate at 24 weeks was higher with intragastric expandable capsules than with placebo using the per protocol set (ETD, 29.6%; P < .001), with similar results using the full analysis set.
• Reduction in fasting insulin levels was higher with intragastric expandable capsules than with placebo (P = .008), while improvements in the lipid profile, fasting plasma glucose levels, and heart rate were similar between the groups.
• Gastrointestinal disorders were reported in 25.0% of participants in the intragastric expandable capsule group compared with 21.9% in the placebo group, with most being transient and mild in severity.

IN PRACTICE:

“As a mild and safe anti-obesity medication, intragastric expandable capsules provide a new therapeutic choice for individuals with overweight or obesity, helping them to enhance and maintain the effect of diet restriction,” wrote the authors.

SOURCE:

Difei Lu, MD, Department of Endocrinology, Peking University First Hospital, Beijing, China, led the study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study included individuals who were overweight or obese, who might have been more willing to lose weight than the general population. Moreover, only 3.25% of the participants had type 2 diabetes, and participants were relatively young. This may have reduced the potential to discover metabolic or cardiovascular improvement by the product.

DISCLOSURES:

This study was funded by Xiamen Junde Pharmaceutical Technology. The authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Persistent hypertriglyceridemia is linked to an increased risk for type 2 diabetes (T2D) in young adults, independent of lifestyle factors.

METHODOLOGY:

• This prospective study analyzed the data of 1,840,251 individuals aged 20-39 years from the South Korean National Health Insurance Service database (mean age 34 years, 71% male).
• The individuals had undergone four consecutive annual health checkups between 2009 and 2012 and had no history of T2D.
• The individuals were sorted into five groups indicating the number of hypertriglyceridemia diagnoses over four consecutive years: 0, 1, 2, 3, and 4, defined as serum fasting triglyceride levels of 150 mg/dL or higher.
• Data on lifestyle-related risk factors, such as smoking status and heavy alcohol consumption, were collected through self-reported questionnaires.
• The primary outcome was newly diagnosed cases of T2D. Over a mean follow-up of 6.53 years, a total of 40,286 individuals developed T2D.

TAKEAWAY:

• The cumulative incidence of T2D increased with an increase in exposure scores for hypertriglyceridemia (log-rank test, P < .001), independent of lifestyle-related factors.
• The incidence rate per 1000 person-years was 1.25 for participants with an exposure score of 0 and 11.55 for those with a score of 4.
• For individuals with exposure scores of 1, 2, 3, and 4, the adjusted hazard ratios for incident diabetes were 1.674 (95% CI, 1.619-1.732), 2.192 (2.117-2.269), 2.637 (2.548-2.73), and 3.715 (3.6-3.834), respectively, vs those with an exposure score of 0.
• Exploratory subgroup analyses suggested the risk for T2D in persistent hypertriglyceridemia were more pronounced among people in their 20s than in their 30s and in women.

IN PRACTICE:

“Identification of individuals at higher risk based on triglyceride levels and management strategies for persistent hypertriglyceridemia in young adults could potentially reduce the burden of young-onset type 2 diabetes and enhance long-term health outcomes,” the authors wrote.

SOURCE:

The study, led by Min-Kyung Lee, Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea, was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

The scoring system based on fasting triglyceride levels of ≥ 150 mg/dL may have limitations, as the cumulative incidence of T2D also varied significantly for mean triglyceride levels. Moreover, relying on a single annual health checkup for hypertriglyceridemia diagnosis might not capture short-term fluctuations. Despite sufficient cases and a high follow-up rate, the study might have underestimated the incidence of T2D.

DISCLOSURES:

This work was supported by the National Research Foundation of Korea grant funded by the Korean Government and the faculty grant of Myongji Hospital. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Persistent hypertriglyceridemia is linked to an increased risk for type 2 diabetes (T2D) in young adults, independent of lifestyle factors.

METHODOLOGY:

• This prospective study analyzed the data of 1,840,251 individuals aged 20-39 years from the South Korean National Health Insurance Service database (mean age 34 years, 71% male).
• The individuals had undergone four consecutive annual health checkups between 2009 and 2012 and had no history of T2D.
• The individuals were sorted into five groups indicating the number of hypertriglyceridemia diagnoses over four consecutive years: 0, 1, 2, 3, and 4, defined as serum fasting triglyceride levels of 150 mg/dL or higher.
• Data on lifestyle-related risk factors, such as smoking status and heavy alcohol consumption, were collected through self-reported questionnaires.
• The primary outcome was newly diagnosed cases of T2D. Over a mean follow-up of 6.53 years, a total of 40,286 individuals developed T2D.

TAKEAWAY:

• The cumulative incidence of T2D increased with an increase in exposure scores for hypertriglyceridemia (log-rank test, P < .001), independent of lifestyle-related factors.
• The incidence rate per 1000 person-years was 1.25 for participants with an exposure score of 0 and 11.55 for those with a score of 4.
• For individuals with exposure scores of 1, 2, 3, and 4, the adjusted hazard ratios for incident diabetes were 1.674 (95% CI, 1.619-1.732), 2.192 (2.117-2.269), 2.637 (2.548-2.73), and 3.715 (3.6-3.834), respectively, vs those with an exposure score of 0.
• Exploratory subgroup analyses suggested the risk for T2D in persistent hypertriglyceridemia were more pronounced among people in their 20s than in their 30s and in women.

IN PRACTICE:

“Identification of individuals at higher risk based on triglyceride levels and management strategies for persistent hypertriglyceridemia in young adults could potentially reduce the burden of young-onset type 2 diabetes and enhance long-term health outcomes,” the authors wrote.

SOURCE:

The study, led by Min-Kyung Lee, Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea, was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

The scoring system based on fasting triglyceride levels of ≥ 150 mg/dL may have limitations, as the cumulative incidence of T2D also varied significantly for mean triglyceride levels. Moreover, relying on a single annual health checkup for hypertriglyceridemia diagnosis might not capture short-term fluctuations. Despite sufficient cases and a high follow-up rate, the study might have underestimated the incidence of T2D.

DISCLOSURES:

This work was supported by the National Research Foundation of Korea grant funded by the Korean Government and the faculty grant of Myongji Hospital. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Persistent hypertriglyceridemia is linked to an increased risk for type 2 diabetes (T2D) in young adults, independent of lifestyle factors.

METHODOLOGY:

• This prospective study analyzed the data of 1,840,251 individuals aged 20-39 years from the South Korean National Health Insurance Service database (mean age 34 years, 71% male).
• The individuals had undergone four consecutive annual health checkups between 2009 and 2012 and had no history of T2D.
• The individuals were sorted into five groups indicating the number of hypertriglyceridemia diagnoses over four consecutive years: 0, 1, 2, 3, and 4, defined as serum fasting triglyceride levels of 150 mg/dL or higher.
• Data on lifestyle-related risk factors, such as smoking status and heavy alcohol consumption, were collected through self-reported questionnaires.
• The primary outcome was newly diagnosed cases of T2D. Over a mean follow-up of 6.53 years, a total of 40,286 individuals developed T2D.

TAKEAWAY:

• The cumulative incidence of T2D increased with an increase in exposure scores for hypertriglyceridemia (log-rank test, P < .001), independent of lifestyle-related factors.
• The incidence rate per 1000 person-years was 1.25 for participants with an exposure score of 0 and 11.55 for those with a score of 4.
• For individuals with exposure scores of 1, 2, 3, and 4, the adjusted hazard ratios for incident diabetes were 1.674 (95% CI, 1.619-1.732), 2.192 (2.117-2.269), 2.637 (2.548-2.73), and 3.715 (3.6-3.834), respectively, vs those with an exposure score of 0.
• Exploratory subgroup analyses suggested the risk for T2D in persistent hypertriglyceridemia were more pronounced among people in their 20s than in their 30s and in women.

IN PRACTICE:

“Identification of individuals at higher risk based on triglyceride levels and management strategies for persistent hypertriglyceridemia in young adults could potentially reduce the burden of young-onset type 2 diabetes and enhance long-term health outcomes,” the authors wrote.

SOURCE:

The study, led by Min-Kyung Lee, Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea, was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

The scoring system based on fasting triglyceride levels of ≥ 150 mg/dL may have limitations, as the cumulative incidence of T2D also varied significantly for mean triglyceride levels. Moreover, relying on a single annual health checkup for hypertriglyceridemia diagnosis might not capture short-term fluctuations. Despite sufficient cases and a high follow-up rate, the study might have underestimated the incidence of T2D.

DISCLOSURES:

This work was supported by the National Research Foundation of Korea grant funded by the Korean Government and the faculty grant of Myongji Hospital. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

People taking a popular type of drug for weight loss or to manage diabetes have a lower likelihood of being newly diagnosed with depression or anxiety, according to an analysis of millions of people’s health records.

The findings were published this week by researchers from the electronic health record company Epic. Researchers looked for new diagnoses of depression or anxiety among people who started taking drugs from a class called GLP-1 agonists that can help manage blood sugar or treat obesity by mimicking hormone levels in the body that can affect appetite and blood sugar. Many people who take the drugs experience significant weight loss.

The researchers found that people with diabetes who started taking most versions of GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than people with diabetes who didn’t take one of the drugs. The greatest reduction in likelihood of a new depression diagnosis was observed among people taking tirzepatide, which is sold under the brand names Mounjaro and Zepbound. 

A reduced likelihood of being diagnosed with anxiety was also observed among people with diabetes after they started taking a GLP-1 agonist, compared to people with diabetes who didn’t take one of the drugs. Again, tirzepatide showed the greatest reduction in odds, with people taking that drug experiencing a 60% reduced likelihood of being newly diagnosed with anxiety.

Similar reductions in the likelihood of new depression or anxiety diagnoses were observed among people who didn’t have diabetes but were taking GLP-1 agonists, such as for weight loss.

The mind-body connection has been well established by research.

“Thoughts, feelings, beliefs, and attitudes can affect how healthy your body is,” according to a summary from the CDC about the connection between diabetes and depression. “Untreated mental health issues can make diabetes worse, and problems with diabetes can make mental health issues worse. But fortunately if one gets better, the other tends to get better, too.”

This latest analysis included the drugs dulaglutide, exenatide, liraglutide, semaglutide, and tirzepatide. The medicines, used for weight loss or to manage diabetes, include the brand names Byetta, Ozempic, Mounjaro, Trulicity, Wegovy, and Zepbound. The researchers also looked for links between depression or anxiety diagnoses among people taking liraglutide (sold under brand names Saxenda and Victoza), but found that there was little to no change in the likelihood of being diagnosed with depression or anxiety after starting liraglutide.

The findings are timely as regulators in the U.S. and Europe are investigating reports of suicidal thoughts among people using the drugs. In January, the FDA announced that a preliminary investigation showed no increased risk of suicidal thoughts or actions, but the agency could not “definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue.”

This latest analysis from Epic Research only looked at health records, was not published in a peer-reviewed journal, nor could it establish a definitive role the medications may have played in whether or not someone was diagnosed with depression or anxiety. It’s unknown whether people in the study had symptoms of depression or anxiety before starting the medications.

“These results show that these medications may serve a dual purpose for patients, but we do not understand them well enough yet to say these medications should be given as a treatment for anxiety or depression outside of diabetes or weight management,” Kersten Bartelt, a researcher employed by Epic, told ABC News.

A version of this article appeared on WebMD.com.

People taking a popular type of drug for weight loss or to manage diabetes have a lower likelihood of being newly diagnosed with depression or anxiety, according to an analysis of millions of people’s health records.

The findings were published this week by researchers from the electronic health record company Epic. Researchers looked for new diagnoses of depression or anxiety among people who started taking drugs from a class called GLP-1 agonists that can help manage blood sugar or treat obesity by mimicking hormone levels in the body that can affect appetite and blood sugar. Many people who take the drugs experience significant weight loss.

The researchers found that people with diabetes who started taking most versions of GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than people with diabetes who didn’t take one of the drugs. The greatest reduction in likelihood of a new depression diagnosis was observed among people taking tirzepatide, which is sold under the brand names Mounjaro and Zepbound. 

A reduced likelihood of being diagnosed with anxiety was also observed among people with diabetes after they started taking a GLP-1 agonist, compared to people with diabetes who didn’t take one of the drugs. Again, tirzepatide showed the greatest reduction in odds, with people taking that drug experiencing a 60% reduced likelihood of being newly diagnosed with anxiety.

Similar reductions in the likelihood of new depression or anxiety diagnoses were observed among people who didn’t have diabetes but were taking GLP-1 agonists, such as for weight loss.

The mind-body connection has been well established by research.

“Thoughts, feelings, beliefs, and attitudes can affect how healthy your body is,” according to a summary from the CDC about the connection between diabetes and depression. “Untreated mental health issues can make diabetes worse, and problems with diabetes can make mental health issues worse. But fortunately if one gets better, the other tends to get better, too.”

This latest analysis included the drugs dulaglutide, exenatide, liraglutide, semaglutide, and tirzepatide. The medicines, used for weight loss or to manage diabetes, include the brand names Byetta, Ozempic, Mounjaro, Trulicity, Wegovy, and Zepbound. The researchers also looked for links between depression or anxiety diagnoses among people taking liraglutide (sold under brand names Saxenda and Victoza), but found that there was little to no change in the likelihood of being diagnosed with depression or anxiety after starting liraglutide.

The findings are timely as regulators in the U.S. and Europe are investigating reports of suicidal thoughts among people using the drugs. In January, the FDA announced that a preliminary investigation showed no increased risk of suicidal thoughts or actions, but the agency could not “definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue.”

This latest analysis from Epic Research only looked at health records, was not published in a peer-reviewed journal, nor could it establish a definitive role the medications may have played in whether or not someone was diagnosed with depression or anxiety. It’s unknown whether people in the study had symptoms of depression or anxiety before starting the medications.

“These results show that these medications may serve a dual purpose for patients, but we do not understand them well enough yet to say these medications should be given as a treatment for anxiety or depression outside of diabetes or weight management,” Kersten Bartelt, a researcher employed by Epic, told ABC News.

A version of this article appeared on WebMD.com.

People taking a popular type of drug for weight loss or to manage diabetes have a lower likelihood of being newly diagnosed with depression or anxiety, according to an analysis of millions of people’s health records.

The findings were published this week by researchers from the electronic health record company Epic. Researchers looked for new diagnoses of depression or anxiety among people who started taking drugs from a class called GLP-1 agonists that can help manage blood sugar or treat obesity by mimicking hormone levels in the body that can affect appetite and blood sugar. Many people who take the drugs experience significant weight loss.

The researchers found that people with diabetes who started taking most versions of GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than people with diabetes who didn’t take one of the drugs. The greatest reduction in likelihood of a new depression diagnosis was observed among people taking tirzepatide, which is sold under the brand names Mounjaro and Zepbound. 

A reduced likelihood of being diagnosed with anxiety was also observed among people with diabetes after they started taking a GLP-1 agonist, compared to people with diabetes who didn’t take one of the drugs. Again, tirzepatide showed the greatest reduction in odds, with people taking that drug experiencing a 60% reduced likelihood of being newly diagnosed with anxiety.

Similar reductions in the likelihood of new depression or anxiety diagnoses were observed among people who didn’t have diabetes but were taking GLP-1 agonists, such as for weight loss.

The mind-body connection has been well established by research.

“Thoughts, feelings, beliefs, and attitudes can affect how healthy your body is,” according to a summary from the CDC about the connection between diabetes and depression. “Untreated mental health issues can make diabetes worse, and problems with diabetes can make mental health issues worse. But fortunately if one gets better, the other tends to get better, too.”

This latest analysis included the drugs dulaglutide, exenatide, liraglutide, semaglutide, and tirzepatide. The medicines, used for weight loss or to manage diabetes, include the brand names Byetta, Ozempic, Mounjaro, Trulicity, Wegovy, and Zepbound. The researchers also looked for links between depression or anxiety diagnoses among people taking liraglutide (sold under brand names Saxenda and Victoza), but found that there was little to no change in the likelihood of being diagnosed with depression or anxiety after starting liraglutide.

The findings are timely as regulators in the U.S. and Europe are investigating reports of suicidal thoughts among people using the drugs. In January, the FDA announced that a preliminary investigation showed no increased risk of suicidal thoughts or actions, but the agency could not “definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue.”

This latest analysis from Epic Research only looked at health records, was not published in a peer-reviewed journal, nor could it establish a definitive role the medications may have played in whether or not someone was diagnosed with depression or anxiety. It’s unknown whether people in the study had symptoms of depression or anxiety before starting the medications.

“These results show that these medications may serve a dual purpose for patients, but we do not understand them well enough yet to say these medications should be given as a treatment for anxiety or depression outside of diabetes or weight management,” Kersten Bartelt, a researcher employed by Epic, told ABC News.

A version of this article appeared on WebMD.com.

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

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

Precision Focus

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

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

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

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

Spanish ‘Prescription Guide’

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

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

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

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

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

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

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

Active Breaks

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

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

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

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

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

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

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

Exerkines and Poly Pills

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

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

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

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

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

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

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

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

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

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

Precision Focus

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

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

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

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

Spanish ‘Prescription Guide’

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

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

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

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

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

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

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

Active Breaks

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

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

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

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

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

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

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

Exerkines and Poly Pills

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

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

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

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

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

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

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

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

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

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

Precision Focus

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

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

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

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

Spanish ‘Prescription Guide’

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

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

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

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

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

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

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

Active Breaks

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

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

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

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

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

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

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

Exerkines and Poly Pills

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Knowns And Unknowns of CGM in Pregnancy

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

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

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

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

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

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

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

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

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

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

CGM in Type 2, GDM

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

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

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

Is Preventing Maternal Hypoglycemia Possible?

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

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

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

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

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

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

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

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

Rethinking Intrapartum Care

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Knowns And Unknowns of CGM in Pregnancy

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

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

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

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

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

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

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

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

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

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

CGM in Type 2, GDM

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

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

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

Is Preventing Maternal Hypoglycemia Possible?

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

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

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

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

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

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

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

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

Rethinking Intrapartum Care

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Knowns And Unknowns of CGM in Pregnancy

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

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

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

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

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

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

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

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

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

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

CGM in Type 2, GDM

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

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

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

Is Preventing Maternal Hypoglycemia Possible?

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

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

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

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

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

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

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

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

Rethinking Intrapartum Care

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

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

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

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

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

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

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

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

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

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

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