GLP-1 receptor agonists in perimenopause and early postmenopause: clinical role, cardiometabolic benefits and knowledge gaps.

Abstract

Perimenopause and early postmenopause represent a critical metabolic transition with adverse changes in body composition, insulin sensitivity, lipid metabolism and cardiometabolic health, contributing to increased rates of obesity, type 2 diabetes and cardiovascular disease. As the prevalence of obesity continues to rise among midlife women, effective therapeutic strategies are increasingly needed. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as highly effective treatments for obesity and type 2 diabetes through their effects on appetite regulation, weight reduction, glucose homeostasis and metabolic health. Beyond their established role, GLP-1 RAs have demonstrated favorable effects on visceral adiposity, glycemic control, lipid profiles, hepatic steatosis and cardiovascular outcomes. Preliminary experimental evidence also suggests possible complementary effects when combined with menopausal hormone therapy (MHT). However, menopause-specific evidence remains limited. This review summarizes the current evidence regarding the efficacy, safety and clinical application of GLP-1 RAs in perimenopausal and early postmenopausal women. Particular attention is given to their effects on cardiometabolic health, cardiovascular risk, bone and muscle health, cancer risk, cognition and potential interactions with MHT. Although GLP-1 RAs represent a promising therapeutic option for obesity and metabolic dysfunction during menopause, important knowledge gaps remain regarding their long-term safety, effects on menopause-related outcomes and optimal integration into comprehensive menopausal care. The efficacy, safety and potential interactions of GLP-1 RAs when used in combination with MHT remain to be determined.