Sex Differences in the Cardiovascular Consequences of Type 2 Diabetes: The Role of Glucose-Lowering Therapy

Women with type 2 diabetes (T2D) experience disproportionately greater cardiovascular risk than men, yet sex-specific differences in the use and effects of glucose-lowering therapies remain underexplored. This narrative review summarizes evidence on prescribing patterns, efficacy, and tolerability of non-insulin antihyperglycemic agents in women versus men. Across most drug classes, glycemic and cardiovascular efficacy appear broadly comparable, though differences in tolerability and prescribing are evident: women more often discontinue metformin, are less frequently prescribed SGLT2 inhibitors despite equal cardio-renal benefit, and are more likely to receive GLP-1 receptor agonists. Sex variations include greater TZD efficacy in obese women, stronger sulfonylurea response in non-obese men, and modestly greater weight loss in women treated with incretin-based therapies. Addressing prescribing disparities and ensuring balanced trial representation remain critical priorities. • Women are more likely than men to discontinue metformin from GI side effects • Women are more likely than men to be prescribed GLP-1 RA and less likely SGLT2i • Most drug classes achieve similar HbA1c reduction and cardiovascular protection between sexes • Impact of sex differences in prescribing on cardiovascular outcomes remains unknown • Balanced trial representation and sex-specific analyses are essential to optimize diabetes care and cardiovascular outcomes