Women's cardiometabolic risk from obesity follows distinct hormonal trajectories—from menarche through menopause—that amplify vulnerability to heart failure with preserved ejection fraction (HFpEF) and ischemia with non-obstructive coronary arteries (INOCA). Conditions unique to women, including pregnancy-related weight retention, hypertensive disorders of pregnancy, and polycystic ovary syndrome (PCOS), compound long-term metabolic damage in ways that standard cardiovascular risk models underestimate. Incretin-based therapies (GLP-1 receptor agonists and dual GIP/GLP-1 agonists) demonstrate meaningful weight loss and cardiovascular benefit, but sex-disaggregated efficacy and tolerability data remain thin.
This review crystallizes a critical blind spot in cardiology: the landmark cardiovascular outcomes trials for GLP-1 agents—LEADER, SUSTAIN-6, SELECT—enrolled predominantly male cohorts, limiting confidence in translating findings directly to women. HFpEF, which disproportionately affects women with obesity, represents a particularly urgent therapeutic frontier where incretin agents show early mechanistic promise but lack powered sex-specific trial data. Additionally, the interaction between GLP-1 agents and hormonal contraception or fertility is inadequately studied, creating real-world prescribing uncertainty. While this is a narrative review rather than a primary trial, its framework usefully consolidates why sex-blind obesity management perpetuates diagnostic and treatment inequities. For clinicians, the practical takeaway is clear: obesity in women demands life-course contextualization, and the cardiovascular benefits of incretin therapies, though compelling, should not be assumed to be equivalent across sexes until dedicated evidence emerges.
