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: 10.13039/501100009293Dementia Australia Yulgilbar Innovation Award.