SGLT2 Inhibitors and Mortality in Endometriosis With Type 2 Diabetes

BACKGROUND: Endometriosis is increasingly recognized as a systemic inflammatory condition associated with adverse cardiovascular events, yet glucose-lowering drug selection in this population is not evidence-based. OBJECTIVES: The purpose of this study was to compare mortality, cardiovascular outcomes, and renal endpoints among adults with endometriosis and type 2 diabetes (T2D) treated with sodium glucose co-transporter 2 inhibitors (SGLT2i) added to background metformin therapy vs metformin-based therapy without SGLT2i. METHODS: We conducted a retrospective cohort study using routinely collected health data. Adults with endometriosis and T2D initiating SGLT2i or receiving metformin-based therapy were identified, and 1:1 propensity score matching was performed. After matching, there were 3,072 patients in each group. The mean follow-up was 2.8 ±1.8 years (median, 2.8; IQR: 3.7). Outcomes were analyzed with time-to-event models and reported as HRs with 95% CIs. RESULTS: In the matched cohort (n = 6,144), all-cause mortality was lower with SGLT2i added to metformin vs metformin-based therapy without SGLT2i (55 vs 115 deaths; 0.65% vs 1.15% per year; HR: 0.52 [95% CI: 0.38-0.72]; P < 0.0001). Rates of ischemic stroke/thromboembolism, acute myocardial infarction, atrial fibrillation, ventricular arrhythmia/cardiac arrest, heart failure, acute pulmonary edema/cardiogenic shock, and peripheral artery disease were not significantly different. Progression to chronic kidney disease stage 4 to 5 was numerically higher with SGLT2i (HR: 1.28 [95% CI: 0.99-1.64]; P = 0.05). CONCLUSIONS: In a propensity-matched analysis of patients with endometriosis and T2D, use of SGLT2i on top of background metformin therapy was associated with lower mortality compared with metformin-based therapy without SGLT2i, with no significant differences in most cardiovascular outcomes.