The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus

Aims/hypothesis Women remain underrepresented in clinical trials and those with type 2 diabetes mellitus are at high risk for cardiovascular (CV) events. The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the risk of CV death or heart failure hospitalisations in individuals with type 2 diabetes. Here, we performed a pre-specified analysis to examine whether sex modifies these effects. Methods The DECLARE-TIMI 58 trial randomised 17,160 patients with type 2 diabetes with or at risk for atherosclerotic disease to dapagliflozin or placebo (median follow-up 4.2 years). The dual efficacy outcomes were CV death or heart failure hospitalisations, and major adverse cardiovascular events (MACE; CV death, myocardial infarction or ischaemic stroke). The renal-specific composite outcome was a sustained >= 40% drop in eGFR to <60 ml min(-1) [1.73 m](-2), new end-stage renal disease or renal death. Cox models were run separately by sex with treatment-by-sex interaction testing for each outcome. Results At baseline, women (n = 6422, 37.4%) had higher HbA(1c), longer type 2 diabetes duration, and were on fewer glucose-lowering medications. There was no evidence of modification of the effect of dapagliflozin by sex for (1) CV death or heart failure hospitalisations: women (3.8% vs 4.5%; HR 0.84, 95% CI 0.66, 1.07) and men (5.3% vs 6.4%; HR 0.83, 95% CI 0.71, 0.96; p(interaction) = 0.90); (2) MACE: women (6.3% vs 6.8%; HR 0.93, 95% CI 0.77, 1.12) and men (10.0% vs 10.7%; HR 0.93, 95% CI 0.83, 1.05; p(interaction) = 0.99); or (3) renal-specific composite: women (1.4% vs 2.8%; HR 0.50, 95% CI 0.35, 0.70) and men (1.5% vs 2.5%; HR 0.55, 95% CI 0.42, 0.73; p(interaction) = 0.64). The overall safety profile of dapagliflozin was similar for women and men. Conclusions/interpretation Dapagliflozin offers comparable CV and renal benefits and a comparable safety profile in women and men.

Automated summary

In this study, it was found that gender did not significantly impact the development of cardiovascular or renal disease in patients with type 2 diabetes treated with dapagliflozin. Furthermore, dapagliflozin showed similar safety and efficacy profiles in women and men.