Incretin-based therapies in menopause: Current landscape

The menopause transition is associated with substantial changes in body composition, including increased central adiposity and accelerated loss of muscle and bone mass, that heighten midlife women's risk of obesity and its cardiometabolic consequences. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide, have emerged as highly effective pharmacotherapies for obesity, and post hoc analyses of pivotal trials suggest that weight-loss efficacy is preserved across reproductive stages, with postmenopausal women achieving reductions in total body weight, waist circumference, and cardiometabolic risk factors comparable to those of premenopausal women. However, the same pharmacologically induced weight loss that drives these benefits raises concern for postmenopausal women, who already experience declines in muscle and bone related to estrogen deficiency that may be exacerbated by weight loss. Current evidence suggests that reductions in lean mass are generally proportional to the magnitude of weight loss but are often accompanied by improved patient-reported physical function. However, lean mass is not synonymous with skeletal muscle function, few trials have assessed muscle strength or objective physical performance as primary outcomes, and findings on bone mineral density and fracture risk remain inconsistent across studies. This review synthesizes current evidence on the use of incretin-based therapies by midlife and postmenopausal women. It specifically addresses weight-loss efficacy, cardiometabolic risk reduction, body composition, and skeletal health, while distinguishing menopause-specific from extrapolated evidence, and indicating the level of evidence supporting clinical considerations for nutrition, exercise, and musculoskeletal monitoring, to guide a menopause-specific approach to incretin-based therapies.