The most consistently documented long-term harm is loss of lean/muscle mass — up to roughly 40% of total weight lost can be fat-free mass — raising sarcopenia risk especially in older adults; however this is measurable and partly mitigable with resistance exercise and adequate protein rather than a contraindication.

Evidence (1)

SEMALEAN: impact of semaglutide on fat mass, lean mass and muscle function

A substantial fraction of semaglutide-induced weight loss is lean mass; magnitude is modifiable by physical activity and diet, motivating monitoring rather than avoidance.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12673431/

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