Annals editorial warns semaglutide and other GLP-1 drugs may add to muscle loss in older adults

An editorial in Annals of Internal Medicine warns that GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy) may add to age-related muscle loss in adults over 65, who have little muscle to spare ^[1]. The editorial, described in a September 18, 2025 report by Endocrine News, calls for assessing muscle mass, physical function and nutrition in older patients and for watching those measures during treatment ^[1].

The editorial is titled "Skeletal Muscle Mass Loss and Glucagon-Like Peptide-1 Receptor Agonists: Are Older Patients at Risk?" and was written by Anjali P. Kakkar and colleagues ^[1].

The concern rests on two sets of numbers. Natural aging reduces skeletal muscle mass by 12% to 16%, the editorial notes, leaving adults over 65 a narrow margin before they cross into frailty ^[1]. Up to half of adults over 80 already have sarcopenia, the age-related loss of muscle mass and strength, which raises the risk of falls, fractures and disability ^[1].

How much of the weight lost on these drugs comes from lean mass is not settled. A 2024 review in Diabetes, Obesity & Metabolism found that 15% to 60% of weight lost on GLP-1 RAs may come from lean mass, depending on the patient and the drug ^[1]. Weight reduction on these medications can exceed 20% of body weight ^[1]. Some of that lean-mass loss may be offset by reductions in fat inside the muscle and by improved muscle quality, but the editorial says older patients may not benefit in the same way, especially if the loss impairs mobility or strength ^[1].

Use of GLP-1 RAs rose from a few thousand to tens of thousands of users nationwide between 2018 and 2022, with older and high-risk patients among them ^[1].

The editorial notes that if patients do not show the expected improvements in function during treatment, skeletal muscle mass loss should be evaluated ^[1]. MRI and CT are considered gold-standard assessments but are costly and not always practical; DEXA scans and bioimpedance analysis are more accessible but vary in quality ^[1].

To counter muscle loss, the editorial's authors recommend pairing GLP-1 use with resistance training and a high-protein diet ^[1]. No drug is currently approved to prevent muscle loss. Eli Lilly and Scholar Rock are developing therapies that aim to combine fat loss with muscle preservation, including myostatin inhibitors and enobosarm ^[1].

The editorial concludes that with planning and tailored support, patients may be able to get the metabolic benefits of these drugs without sacrificing strength, mobility or quality of life ^[1].

Why it matters for patients

For older adults taking or considering these medications, the practical question is how much of the weight lost is fat and how much is muscle. Losing muscle can affect strength, balance and the ability to live independently, and the editorial warns that medication-related loss could push some patients into frailty ^[1].

Because the share of lean mass lost varies widely in the research cited — 15% to 60% — the editorial argues the risk should be judged patient by patient rather than assumed to be the same for everyone ^[1].

The editorial also draws attention to how muscle is measured. MRI and CT are the most reliable methods but are expensive and not routine, while DEXA and bioimpedance are easier to obtain but differ in quality, so results may not be comparable from one clinic to another ^[1].

Since no medication is approved to protect muscle during weight loss, the strategies discussed in the editorial are resistance training and adequate protein ^[1]. The editorial does not specify protein targets or exercise regimens, and it does not cite trials in older GLP-1 users that test those approaches.

What happens next

The editorial calls for more personalized care for older patients: assessing baseline muscle mass, physical function and nutrition before prescribing a GLP-1 RA, then monitoring during treatment ^[1]. Whether regulators or medical societies will issue specific guidance on muscle monitoring for older GLP-1 users has not been reported. No timeline has been disclosed for the muscle-preservation therapies in development at Eli Lilly and Scholar Rock, and none of those products is approved ^[1].