Protein Safeguards Muscle in Semaglutide Weight-Loss Therapy

TOPLINE:

In adults with obesity who were prescribed semaglutide, older age and female sex were associated with greater muscle loss, whereas a higher protein intake appeared to be protective against this loss. Greater muscle loss was independently linked to diminished glycemic benefits of the drug.

METHODOLOGY:

• When adults with obesity lose weight, they often lose muscle mass, with about 40% of the weight lost with semaglutide, a GLP-1 receptor agonist, being lean tissue. However, predictors of muscle loss and its effects on glucose and bone homeostasis remain unclear.
• Researchers conducted a prospective observational study to identify risk and protective factors for the loss of muscle mass during semaglutide-induced weight loss and to assess its effect on glucose and bone homeostasis.
• They included 40 adults with obesity (mean age, 46 years; 73% women; mean BMI, 36.8) who received either semaglutide (n = 23) or a diet and lifestyle intervention (n = 17) for 3 months.
• The primary outcome was a change in lean mass, measured using DEXA.

TAKEAWAY:

• The mean weight loss was significantly greater in the semaglutide group than in the diet and lifestyle intervention group (6.3% vs 2.5%; P = .002), but the proportion of weight loss attributed to lean mass did not differ between groups (P = .39).
• A change in lean mass showed a stronger correlation with weight change in the diet and lifestyle intervention group (correlation coefficient [R], 0.93; P < .0001) than in the semaglutide group (R, 0.55; P = .01).
• Older age (P = .046), female sex (P = .02), and lower protein intake at 3 months (P = .03) were linked to a greater decrease in lean mass at 3 months in the semaglutide group but not in the diet and lifestyle intervention group.
• A greater loss of lean mass was also linked to smaller improvements in glycemic control in the semaglutide group only.

IN PRACTICE:

“Maintaining muscle mass with weight loss in individuals with obesity on semaglutide may be essential to mitigate insulin resistance and frailty,” the authors of the study wrote.

SOURCE:

The study was led by Melanie Haines, MD, of Massachusetts General Hospital and Harvard Medical School in Boston. It was presented on July 12, 2025, at ENDO 2025: The Endocrine Society Annual Meeting in San Francisco.

LIMITATIONS:

This abstract did not discuss any limitations.

DISCLOSURES:

This abstract did not report any specific funding or conflicts of interest.

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