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ENDO: Older Age, Female Sex Tied to Greater Muscle Loss With Semaglutide

By Lori Solomon HealthDay Reporter

Medically reviewed by Carmen Pope, BPharm. Last updated on July 17, 2025.

via HealthDay

THURSDAY, July 17, 2025 -- Older age and female sex may be associated with greater muscle loss in adults with obesity prescribed semaglutide, and greater muscle loss is independently associated with less improvement in glucose homeostasis, according to a study presented at ENDO 2025, the annual meeting of the Endocrine Society, held from July 12 to 15 in San Francisco.

Melanie S. Haines, M.D., from Massachusetts General Hospital in Boston, and colleagues conducted an observational prospective study to identify risk factors for and factors that protect against loss of muscle mass due to weight loss with semaglutide. The analysis included 40 adults with obesity who were prescribed either semaglutide (23 individuals) or a diet and lifestyle intervention for weight loss (Healthy Habits for Life [HHL]; 17 individuals) for three months.

The researchers found that mean weight loss was 6.3 percent with semaglutide versus 2.5 percent with HHL. Nearly half of the weight loss (47.5 percent) was lean mass in the semaglutide group versus 35.7 percent in the HHL group. At three months, lower protein intake in the semaglutide group (R = 0.52) and older age in the HHL group (R = −0.53) were associated with a greater decrease in lean mass. Older age, female sex, and lower protein intake at three months were associated with a greater decrease in lean mass in the semaglutide group but not the HHL group when adjusting for change in weight. A greater decrease in lean mass was associated with less improvement in glycated hemoglobin in an adjusted analysis in the semaglutide group only. In the semaglutide group only, the bone resorption marker C-terminal telopeptide (15 percent) and total body bone mineral density (1.8 percent) increased.

"Older adults and women may be more likely to lose muscle on semaglutide, but eating more protein may help protect against this," Haines said in a statement. "Losing too much muscle may reduce the benefits of semaglutide on blood sugar control. This means preserving muscle during weight loss with semaglutide may be important to reduce insulin resistance and prevent frailty in people with obesity."

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