Obesity

Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But ongoing shortages expected to last until the end of this year combined with increasing demand have raised ethical questions about who deserves access to the drugs.

Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.

The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.

As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
 

Sweden

Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.

Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.

“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.

Providers are being forced to prioritize some patients above others, she added.

“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”

Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.

In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.

“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
 

United Kingdom

Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.

In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.

Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.

“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.

Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.

He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
 

United States

Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.

In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.

According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.

On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.

Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.

The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.

If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.

“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.

For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
 

Canada

The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.

About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.

He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.

Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.

“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
 

What Are the Alternatives?

In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.

“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”

Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.

“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But ongoing shortages expected to last until the end of this year combined with increasing demand have raised ethical questions about who deserves access to the drugs.

Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.

The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.

As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
 

Sweden

Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.

Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.

“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.

Providers are being forced to prioritize some patients above others, she added.

“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”

Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.

In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.

“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
 

United Kingdom

Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.

In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.

Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.

“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.

Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.

He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
 

United States

Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.

In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.

According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.

On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.

Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.

The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.

If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.

“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.

For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
 

Canada

The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.

About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.

He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.

Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.

“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
 

What Are the Alternatives?

In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.

“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”

Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.

“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But ongoing shortages expected to last until the end of this year combined with increasing demand have raised ethical questions about who deserves access to the drugs.

Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.

The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.

As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
 

Sweden

Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.

Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.

“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.

Providers are being forced to prioritize some patients above others, she added.

“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”

Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.

In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.

“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
 

United Kingdom

Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.

In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.

Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.

“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.

Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.

He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
 

United States

Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.

In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.

According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.

On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.

Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.

The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.

If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.

“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.

For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
 

Canada

The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.

About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.

He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.

Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.

“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
 

What Are the Alternatives?

In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.

“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”

Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.

“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.

A version of this article appeared on Medscape.com.

If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.

In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.

How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.

“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.

Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.

These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.

The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.

The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.

How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?

It’s possible…
 

CR Mimetics: The Healthspan Drug?

CR mimetics, despite the easy assumption to make, aren’t really for weight loss. Not to muscle in on the GLP-1 turf, the CR drugs’ wheelhouse appears to be extending healthspan.

From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.

Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”

That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.

Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”

Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.

Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.

Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.

“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
 

Exercise Mimetics: Fitness in a Pill?

Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.

Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.

In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.

Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.

At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
 

The Future of Exercise and CR Pills

The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.

But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”

Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.

Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”

And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?

Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”

A version of this article appeared on Medscape.com.

If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.

In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.

How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.

“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.

Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.

These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.

The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.

The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.

How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?

It’s possible…
 

CR Mimetics: The Healthspan Drug?

CR mimetics, despite the easy assumption to make, aren’t really for weight loss. Not to muscle in on the GLP-1 turf, the CR drugs’ wheelhouse appears to be extending healthspan.

From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.

Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”

That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.

Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”

Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.

Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.

Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.

“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
 

Exercise Mimetics: Fitness in a Pill?

Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.

Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.

In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.

Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.

At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
 

The Future of Exercise and CR Pills

The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.

But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”

Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.

Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”

And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?

Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”

A version of this article appeared on Medscape.com.

If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.

In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.

How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.

“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.

Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.

These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.

The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.

The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.

How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?

It’s possible…
 

CR Mimetics: The Healthspan Drug?

CR mimetics, despite the easy assumption to make, aren’t really for weight loss. Not to muscle in on the GLP-1 turf, the CR drugs’ wheelhouse appears to be extending healthspan.

From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.

Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”

That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.

Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”

Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.

Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.

Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.

“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
 

Exercise Mimetics: Fitness in a Pill?

Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.

Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.

In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.

Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.

At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
 

The Future of Exercise and CR Pills

The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.

But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”

Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.

Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”

And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?

Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”

A version of this article appeared on Medscape.com.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.

METHODOLOGY:

• Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
• Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
• Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.

TAKEAWAY:

• During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
• Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
• For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
• When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
• An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.

IN PRACTICE:

“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.

SOURCE:

The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.

DISCLOSURES:

One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients on weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have high residual gastric content, a major risk factor for aspiration under anesthesia, despite following fasting guidelines before undergoing elective procedures.

METHODOLOGY:

• The increasing use of GLP-1 RAs to manage weight and hyperglycemia has sparked safety concerns because of the drugs’ association with slow gastric emptying, a major risk factor for aspiration under anesthesia.
• This cross-sectional study used gastric ultrasonography to examine the link between GLP-1 RA use and the prevalence of increased residual gastric content.
• All 124 participants (median age, 56 years; 60% women) — half of whom received once-weekly GLP-1 RAs such as semaglutide, dulaglutide, or tirzepatide — adhered to the guideline-recommended fasting duration before undergoing elective procedures under anesthesia.
• The primary outcome focused on identifying increased residual gastric content, defined by the presence of solids, thick liquids, or > 1.5 mL/kg of clear liquids on ultrasound.
• An exploratory analysis examined the association between the duration of GLP-1 RA discontinuation and increased residual gastric content.

TAKEAWAY:

• The adjusted prevalence of increased residual gastric content was 30.5% (95% CI, 9.9%-51.2%) higher in participants who received GLP-1 RA than those who did not.
• Most patients took their last dose of GLP-1 RA within 5 days before their procedure, but elevated residual gastric content persisted even after 7 days of GLP-1 RA discontinuation.
• There was also no significant association between the type of GLP-1 RA used and the prevalence of increased residual gastric content.

IN PRACTICE:

“We expect healthcare professionals will encounter these classes of drugs with increasing frequency in the perioperative period. Perioperative physicians, including anesthesiologists, surgeons, and primary care physicians, should be well-informed about the safety implications of GLP-1 RA drugs,” the authors wrote.

SOURCE:

The study was led by Sudipta Sen, MD, from the Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Center at Houston, Houston, Texas, and published online in JAMA Surgery.

LIMITATIONS:

Residual gastric content, the primary outcome, served as a proxy for aspiration risk and does not have an exact threshold of volume associated with increased risk. The study did not directly evaluate aspiration events. The authors also acknowledged potential bias from unmeasured confounders owing to the observational nature of this study. A small sample size limited the ability to detect a risk difference for each additional day of drug discontinuation before surgery.

DISCLOSURES:

One of the authors reported receiving a grant from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients on weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have high residual gastric content, a major risk factor for aspiration under anesthesia, despite following fasting guidelines before undergoing elective procedures.

METHODOLOGY:

• The increasing use of GLP-1 RAs to manage weight and hyperglycemia has sparked safety concerns because of the drugs’ association with slow gastric emptying, a major risk factor for aspiration under anesthesia.
• This cross-sectional study used gastric ultrasonography to examine the link between GLP-1 RA use and the prevalence of increased residual gastric content.
• All 124 participants (median age, 56 years; 60% women) — half of whom received once-weekly GLP-1 RAs such as semaglutide, dulaglutide, or tirzepatide — adhered to the guideline-recommended fasting duration before undergoing elective procedures under anesthesia.
• The primary outcome focused on identifying increased residual gastric content, defined by the presence of solids, thick liquids, or > 1.5 mL/kg of clear liquids on ultrasound.
• An exploratory analysis examined the association between the duration of GLP-1 RA discontinuation and increased residual gastric content.

TAKEAWAY:

• The adjusted prevalence of increased residual gastric content was 30.5% (95% CI, 9.9%-51.2%) higher in participants who received GLP-1 RA than those who did not.
• Most patients took their last dose of GLP-1 RA within 5 days before their procedure, but elevated residual gastric content persisted even after 7 days of GLP-1 RA discontinuation.
• There was also no significant association between the type of GLP-1 RA used and the prevalence of increased residual gastric content.

IN PRACTICE:

“We expect healthcare professionals will encounter these classes of drugs with increasing frequency in the perioperative period. Perioperative physicians, including anesthesiologists, surgeons, and primary care physicians, should be well-informed about the safety implications of GLP-1 RA drugs,” the authors wrote.

SOURCE:

The study was led by Sudipta Sen, MD, from the Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Center at Houston, Houston, Texas, and published online in JAMA Surgery.

LIMITATIONS:

Residual gastric content, the primary outcome, served as a proxy for aspiration risk and does not have an exact threshold of volume associated with increased risk. The study did not directly evaluate aspiration events. The authors also acknowledged potential bias from unmeasured confounders owing to the observational nature of this study. A small sample size limited the ability to detect a risk difference for each additional day of drug discontinuation before surgery.

DISCLOSURES:

One of the authors reported receiving a grant from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients on weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have high residual gastric content, a major risk factor for aspiration under anesthesia, despite following fasting guidelines before undergoing elective procedures.

METHODOLOGY:

• The increasing use of GLP-1 RAs to manage weight and hyperglycemia has sparked safety concerns because of the drugs’ association with slow gastric emptying, a major risk factor for aspiration under anesthesia.
• This cross-sectional study used gastric ultrasonography to examine the link between GLP-1 RA use and the prevalence of increased residual gastric content.
• All 124 participants (median age, 56 years; 60% women) — half of whom received once-weekly GLP-1 RAs such as semaglutide, dulaglutide, or tirzepatide — adhered to the guideline-recommended fasting duration before undergoing elective procedures under anesthesia.
• The primary outcome focused on identifying increased residual gastric content, defined by the presence of solids, thick liquids, or > 1.5 mL/kg of clear liquids on ultrasound.
• An exploratory analysis examined the association between the duration of GLP-1 RA discontinuation and increased residual gastric content.

TAKEAWAY:

• The adjusted prevalence of increased residual gastric content was 30.5% (95% CI, 9.9%-51.2%) higher in participants who received GLP-1 RA than those who did not.
• Most patients took their last dose of GLP-1 RA within 5 days before their procedure, but elevated residual gastric content persisted even after 7 days of GLP-1 RA discontinuation.
• There was also no significant association between the type of GLP-1 RA used and the prevalence of increased residual gastric content.

IN PRACTICE:

“We expect healthcare professionals will encounter these classes of drugs with increasing frequency in the perioperative period. Perioperative physicians, including anesthesiologists, surgeons, and primary care physicians, should be well-informed about the safety implications of GLP-1 RA drugs,” the authors wrote.

SOURCE:

The study was led by Sudipta Sen, MD, from the Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Center at Houston, Houston, Texas, and published online in JAMA Surgery.

LIMITATIONS:

Residual gastric content, the primary outcome, served as a proxy for aspiration risk and does not have an exact threshold of volume associated with increased risk. The study did not directly evaluate aspiration events. The authors also acknowledged potential bias from unmeasured confounders owing to the observational nature of this study. A small sample size limited the ability to detect a risk difference for each additional day of drug discontinuation before surgery.

DISCLOSURES:

One of the authors reported receiving a grant from the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

TOPLINE:

The anti-inflammatory shift in mid-pregnancy may be linked to changes in gut microbiota, which, in turn, may wield their influence through fecal and plasma metabolites.

METHODOLOGY:

• Midway through a normal pregnancy, the maternal immune system shifts to a more anti-inflammatory state, which may be linked to changes in the gut microbial community by unknown mechanisms.
• The study explored the associations between the gut microbiota, fecal and plasma metabolites, and cytokine levels of pregnant women and compared them with those of nonpregnant women.
• The study recruited 30 pregnant women (ages 18-34 years; prepregnancy body mass index [BMI], 18.5-21.9) who conceived naturally with a singleton pregnancy and 15 nonpregnant women of similar age and BMI from the First Affiliated Hospital of Jinan University, Guangzhou, China, between February 2019 and August 2020.
• All participants had not used probiotics or antibiotics in the 6 months prior to participating in the study.
• Fecal and blood samples were collected during or after the 37th week of pregnancy in pregnant women until their labor and on the 14th day of the menstrual cycle in nonpregnant women.

TAKEAWAY:

• Pregnant women had more Actinobacteriota than nonpregnant women (9.15% vs 2.98%, respectively; P = .002) in their gut microbiomes, and the most enriched other microbes showed a negative correlation with pro-inflammatory cytokines.
• Pregnant women had differences in 44 fecal and 53 plasma metabolites, with certain enriched metabolites negatively correlated with pro-inflammatory cytokines and certain depleted ones positively correlated.
• Levels of pro-inflammatory plasma cytokines such as interleukins (IL)-1β, IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor alpha were reduced, while levels of the anti-inflammatory cytokine IL-4 were elevated in pregnant vs nonpregnant women.
• Researchers identified a total of 46 connections between gut microbes, metabolites, and cytokines, with details suggesting that gut microbes may alter plasma cytokine levels by interacting with host metabolites.

IN PRACTICE:

“Our study revealed complicated associations among gut microbiota, metabolites, and immune system during pregnancy and identified some specific metabolites which may act as mediators between symbiotic microorganisms and immune homeostasis,” the authors wrote.

SOURCE:

The study, led by Ting Huang, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, China, was published online on February 7, 2024, in mSystems.

LIMITATIONS:

The small sample size of the study may have limited capacity to address errors resulting from individual differences. No causal relationships between gut microbiota, metabolites, and immune system response could be confirmed. Researchers were unable to account for the possible effects of confounding variables, such as diet, because of the cross-sectional nature of this study.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

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

TOPLINE:

The anti-inflammatory shift in mid-pregnancy may be linked to changes in gut microbiota, which, in turn, may wield their influence through fecal and plasma metabolites.

METHODOLOGY:

• Midway through a normal pregnancy, the maternal immune system shifts to a more anti-inflammatory state, which may be linked to changes in the gut microbial community by unknown mechanisms.
• The study explored the associations between the gut microbiota, fecal and plasma metabolites, and cytokine levels of pregnant women and compared them with those of nonpregnant women.
• The study recruited 30 pregnant women (ages 18-34 years; prepregnancy body mass index [BMI], 18.5-21.9) who conceived naturally with a singleton pregnancy and 15 nonpregnant women of similar age and BMI from the First Affiliated Hospital of Jinan University, Guangzhou, China, between February 2019 and August 2020.
• All participants had not used probiotics or antibiotics in the 6 months prior to participating in the study.
• Fecal and blood samples were collected during or after the 37th week of pregnancy in pregnant women until their labor and on the 14th day of the menstrual cycle in nonpregnant women.

TAKEAWAY:

• Pregnant women had more Actinobacteriota than nonpregnant women (9.15% vs 2.98%, respectively; P = .002) in their gut microbiomes, and the most enriched other microbes showed a negative correlation with pro-inflammatory cytokines.
• Pregnant women had differences in 44 fecal and 53 plasma metabolites, with certain enriched metabolites negatively correlated with pro-inflammatory cytokines and certain depleted ones positively correlated.
• Levels of pro-inflammatory plasma cytokines such as interleukins (IL)-1β, IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor alpha were reduced, while levels of the anti-inflammatory cytokine IL-4 were elevated in pregnant vs nonpregnant women.
• Researchers identified a total of 46 connections between gut microbes, metabolites, and cytokines, with details suggesting that gut microbes may alter plasma cytokine levels by interacting with host metabolites.

IN PRACTICE:

“Our study revealed complicated associations among gut microbiota, metabolites, and immune system during pregnancy and identified some specific metabolites which may act as mediators between symbiotic microorganisms and immune homeostasis,” the authors wrote.

SOURCE:

The study, led by Ting Huang, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, China, was published online on February 7, 2024, in mSystems.

LIMITATIONS:

The small sample size of the study may have limited capacity to address errors resulting from individual differences. No causal relationships between gut microbiota, metabolites, and immune system response could be confirmed. Researchers were unable to account for the possible effects of confounding variables, such as diet, because of the cross-sectional nature of this study.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

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

TOPLINE:

The anti-inflammatory shift in mid-pregnancy may be linked to changes in gut microbiota, which, in turn, may wield their influence through fecal and plasma metabolites.

METHODOLOGY:

• Midway through a normal pregnancy, the maternal immune system shifts to a more anti-inflammatory state, which may be linked to changes in the gut microbial community by unknown mechanisms.
• The study explored the associations between the gut microbiota, fecal and plasma metabolites, and cytokine levels of pregnant women and compared them with those of nonpregnant women.
• The study recruited 30 pregnant women (ages 18-34 years; prepregnancy body mass index [BMI], 18.5-21.9) who conceived naturally with a singleton pregnancy and 15 nonpregnant women of similar age and BMI from the First Affiliated Hospital of Jinan University, Guangzhou, China, between February 2019 and August 2020.
• All participants had not used probiotics or antibiotics in the 6 months prior to participating in the study.
• Fecal and blood samples were collected during or after the 37th week of pregnancy in pregnant women until their labor and on the 14th day of the menstrual cycle in nonpregnant women.

TAKEAWAY:

• Pregnant women had more Actinobacteriota than nonpregnant women (9.15% vs 2.98%, respectively; P = .002) in their gut microbiomes, and the most enriched other microbes showed a negative correlation with pro-inflammatory cytokines.
• Pregnant women had differences in 44 fecal and 53 plasma metabolites, with certain enriched metabolites negatively correlated with pro-inflammatory cytokines and certain depleted ones positively correlated.
• Levels of pro-inflammatory plasma cytokines such as interleukins (IL)-1β, IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor alpha were reduced, while levels of the anti-inflammatory cytokine IL-4 were elevated in pregnant vs nonpregnant women.
• Researchers identified a total of 46 connections between gut microbes, metabolites, and cytokines, with details suggesting that gut microbes may alter plasma cytokine levels by interacting with host metabolites.

IN PRACTICE:

“Our study revealed complicated associations among gut microbiota, metabolites, and immune system during pregnancy and identified some specific metabolites which may act as mediators between symbiotic microorganisms and immune homeostasis,” the authors wrote.

SOURCE:

The study, led by Ting Huang, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, China, was published online on February 7, 2024, in mSystems.

LIMITATIONS:

The small sample size of the study may have limited capacity to address errors resulting from individual differences. No causal relationships between gut microbiota, metabolites, and immune system response could be confirmed. Researchers were unable to account for the possible effects of confounding variables, such as diet, because of the cross-sectional nature of this study.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

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

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.