Sex Differences in Risk of Cardiovascular Events and Mortality with Sodium Glucose Co-Transporter-2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Australians with Type 2 Diabetes: a Population-Based Cohort Study

Background Sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D). Despite known sex differences in diabetes-induced cardiovascular disease (CVD), pharmacological treatment recommendations are independent of sex. Our objective was to investigate possible sex differences in rates of MACE with SGLT2i vs. GLP-1RA use. Methods This population-based cohort study included men and women with T2D (>= 30 years), discharged from a Victorian hospital between 1st July 2013 and 1st July 2017, and dispensed an SGLT2i or GLP-1RA within 60 days of discharge. Using Cox proportional hazards regression with competing risks, subdistribution hazard ratios (sHR) with 95% confidence intervals (CI) were estimated for MACE in a follow-up to 30th June 2018. Analyses were conducted for men and women, and subgroups based on age, baseline heart failure (HF), and atherosclerotic CVD (ASCVD) status. Findings From a total of 8026 people (44.3% women, median follow-up time = 756 days), SGLT2i (n = 4231), compared to GLP-1RAs (n = 3795), reduced MACE rates in men (sHR 0.78; 95%CI 0.66-0.93), but not women. SGLT2i reduced MACE rates in men (sHR 0.72; 95%CI 0.54-0.98) and women (sHR 0.52; 95%CI 0.31-0.86) >= 65 years; in men with baseline HF (sHR 0.45; 95%CI 0.28-0.73); and in women with ASCVD (sHR 0.36; 95%CI 0.18-0.71). Interpretations SGLT2i, relative to GLP-1RAs, demonstrate favourable effects for MACE reductions among older Australian men and women with T2D. Analogous benefits were also observed in men with HF and women with ASCVD. Funding Dementia Australia Yulgilbar Innovation Award. Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).