Glucagon-like peptide-1 receptor agonists and muscle strength changes in older adults: Risks beyond muscle mass reductions.

Gastric inhibitory polypeptide (GIP)/Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for the management of obesity and type 2 diabetes, yet research pertinent to their effects on muscle health is limited. Considering the central role of muscle strength as a sarcopenia component, this article summarizes emerging evidence on insulin-based therapies and muscle strength. Short-to-mid-term trials of semaglutide or liraglutide in adults with obesity have shown statistically preserved handgrip strength despite reductions in lean soft tissue mass, suggesting that muscle strength may not decline proportionally to weight loss. Likewise, tirzepatide combined with resistance and aerobic training in young men may not confer additional strength benefits beyond exercise alone. In contrast, longitudinal and retrospective research in older adults with type 2 diabetes have reported reductions in handgrip strength and accelerated sarcopenia with prolonged semaglutide use, raising concerns about potentially detrimental effects on neuromuscular health. Collectively, these findings indicate that lean soft tissue loss is not a reliable predictor of muscle strength change following GIP/GLP-1 agonists. While shorter term studies suggest relative preservation, longer term data in older adults point to possible risk of muscle strength decline. Future randomized, double-blinded trials with adequate sample sizes and longer follow-ups are warranted, particularly in older populations who are at an increased risk of sarcopenia. Their findings could support the integration of muscle strength outcomes into clinical monitoring and trial design to ensure that GIP/GLP-1 agonist-based strategies may not compromise muscle strength in these populations during weight loss.