Sex differences in cardiovascular and renal outcomes with sodium–glucose cotransporter 2 inhibitors: a meta-analysis of randomized controlled trials

Abstract Background Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy in reducing adverse cardiovascular (CV) and renal events in several randomized controlled trials (RCTs). However, women represent a minority of the participants in these RCTs, and how the effects of SGLT2i differ between men and women remains unclear. Methods The MEDLINE and EMBASE databases and the Cochrane library were searched to identify studies published before September 16, 2022. RCTs comparing SGLT2i with placebo and reporting CV or renal outcomes were included. Outcomes of interest included all-cause death, CV death, hospitalization for heart failure (HHF), the composite outcome of CV death and HHF, the composite outcome of major adverse cardiac events (MACE), the composite renal outcome, and the composite of renal outcomes and CV death. Risk ratios of each outcome were pooled using a random-effects model. Subgroup analyses were performed to examine composite renal outcomes in those with pre-existing chronic kidney disease (CKD) and composite HHF outcomes in those with pre-existing heart failure (HF). Results In both women and men, SGLT2i use was associated with lower risks of the composite of CV death and HHF, HHF, MACE, the composite renal outcome, and the composite of renal outcome and CV death. No significant differences in SGLT2i treatment effects were identified between women and men for any outcome. Conclusions SGLT2i provide consistent CV and renal protection for both women and men. These benefits persisted across subgroups of patients with pre-existing HF or CKD. PROSPERO registration number : CRD42022319335.