Where do indications for GLP-1 receptor agonists (RAs) currently stand? Experts addressed these questions at the French Nutrition Days 2025 in Lyon, France, with a focus on obesity treatment, sarcopenia, and mental health.

Opening the session, Bérénice Segrestin, MD, from the Department of Endocrinology, Diabetes and Nutrition, Hospices Civils de Lyon in Lyon, France, described her involvement in a position paper aimed at structuring treatment pathways around antiobesity medications.

“This initiative, coordinated by Judith Aron-Wisnewsky, MD, PhD, of the Nutrition Department at Pitié Salpêtrière Hospital, Sorbonne University, Paris, and Emmanuel Disse, MD, PhD, of the Endocrinology, Diabetes Nutrition Department at Hospices Civils de Lyon in Lyon, France, aims to support weight loss beyond pharmacologic treatment alone,” she said.

GLP-1 RAs are “at the center of a global surge,” Segrestin noted, with prescriptions rising sharply, particularly in the US, where 1 in 8 adults received a prescription in 2024. The market is projected to reach $100 billion by 2030.

Treatment Discontinuation

Several GLP-1 RAs are available or under development, including semaglutide in oral and injectable forms, tirzepatide, and other phase 3 agents. A weight loss of up to 24% has been reported with tirzepatide for approximately 72 weeks.

Treatment typically includes a 12-month weight-loss phase, followed by long-term treatment to maintain the results. “The main challenge is maintaining treatment,” Segrestin said. “Two thirds of patients regain weight after discontinuation.”

In a recent study of 125,474 patients in the US, nearly 50% discontinued treatment. Factors associated with discontinuation included the absence of diabetes, older age, poor gastrointestinal tolerance, and greater socioeconomic vulnerability.

Clinical Recommendations

According to Segrestin, the European Association for the Study of Obesity recommends selecting antiobesity treatment based on adiposity-related complications rather than weight loss alone.

“Tirzepatide appears preferable for obstructive sleep apnea, while semaglutide is recommended in advanced knee osteoarthritis,” she said. “For heart failure or cardiovascular prevention, either agent may be considered based on available evidence.”

GLP-1 RAs are indicated as second-line therapy in patients with a BMI of 27 with complications or 30 without complications. Careful patient selection and treatment are essential.

Segrestin emphasized the multidisciplinary approach: The physician nutrition specialist prescribes and monitors treatment, while dietitians play a key role before and during therapy by adjusting dietary advice according to tolerance.

She also warned about an increased risk for gallstones and recommended abdominal ultrasonography and preventive use of ursodeoxycholic acid depending on the presence or absence of gallstones.

Sarcopenia Concerns

Chloe Amouyal Galand, MD,PhD, from Assistance Publique-Hôpitaux de Paris, Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital in Paris, France, addressed the relationship between sarcopenia and GLP-1 analogues.

“Sarcopenia, defined as a reduction in muscle mass and function, is a critical issue in patients with obesity treated with GLP-1 RAs, particularly in older adults,” she said.

Randomized trials involving semaglutide (STEP 1, SUSTAIN 8), tirzepatide (SURMOUNT-1), and liraglutide have shown that lean mass reduction ranged from 0% to 13%. The observed lean mass loss exceeds that expected with aging alone and is comparable to approximately 10 years of muscle aging.

Meta-analyses indicated that lean mass accounts for about 25% of total weight loss, a proportion similar to that observed after bariatric surgery.

Mental Health Implications

Ophélia Godin, PhD, from the Translational Psychiatry team at Mondor Institute for Biomedical Research, and researcher at French Institute of Health and Medical Research, Créteil, France, discussed the potential role of GLP-1 RAs in mental health.

“Life expectancy in individuals with psychiatric disorders is reduced by 13-16 years, mainly due to cardiovascular disease related to obesity and psychotropic adverse effects such as weight gain, diabetes, and dyslipidemia,” she said.

A recent meta-analysis including over 543 patients with severe psychiatric disorders reported a mean weight loss of 5 kg for GLP-1 RAs, with tolerability similar to that of the general population.

These agents may also have neuroprotective effects by acting on the brain regions involved in mood and anxiety. Several studies have reported reductions in depressive symptoms, although data remain limited.

Regarding addiction, particularly alcohol use, animal and human studies suggest reduced consumption and fewer alcohol related hospitalizations, with stronger effects in individuals with overweight and in men.

“GLP-1 RAs help reduce craving episodes and improve control over eating behavior,” Godin said. However, approximately 30% of people with obesity have a comorbid eating disorder, and GLP-1 RAs may worsen the eating disorder itself.

This story was translated from Univadis France, part of the Medscape Professional Network.