Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) remain underused in routine practice, particularly among women. Aim: This study evaluated gender differences in mortality among patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) and examined whether disparities in SGLT2i and GLP-1RA dispensing contribute to mortality. Methods: The CARDIAB cohort included 138,397 patients with T2DM and established ASCVD, categorized by gender into male and female groups. The primary endpoint was all-cause mortality, and the secondary outcome was the dispensing rates of SGLT2i and GLP-1RA. Results: Of the 138,397 patients, 40.3% were women and 59.7% were men. The overall dispensing rates of SGLT2i and GLP-1RA were 37.1% and 23.4%, respectively, and were significantly lower among women compared with men for both SGLT2i (27.8% vs. 43.3%; p < 0.001) and GLP-1RA (21.3% vs. 24.9%; p < 0.001). Women exhibited higher mortality rates, as reflected by deaths per 10,000 patient-years (9724 vs. 7744; p < 0.001). However, in multivariable analysis, gender was not an independent predictor of mortality. Notably, the use of cardioprotective medications was strongly associated with reduced mortality, with the greatest benefit observed for SGLT2i (HR 0.307; 95% CI 0.299-0.316; p < 0.001) and GLP-1RA (HR 0.466; 95% CI 0.451-0.482; p < 0.001). Conclusions: Women with T2DM and ASCVD were treated less often with SGLT2i and GLP-1RA, therapies strongly associated with lower mortality. Their higher unadjusted mortality appears to reflect undertreatment rather than sex-related risk. Action is needed to improve the use of these cardioprotective medications, especially in women.