Uric acid-lowering effects of sodium-glucose cotransporter 2 inhibitors for preventing cardiovascular events and mortality: A systematic review and meta-analysis

Abstract

Background: To evaluate the effect of a 1 mg/dl reduction in uric acid (UA) on cardiovascular events and mortality in patients treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Research Design and Methods: We performed a systematic review of the MEDLINE and EMBASE databases searched up to 30 June 2023 (PROSPERO, CRD42022355479) to identify large-scale SGLT2 inhibitor trials. Random-effects meta-analyses were used to pool the estimates. Results: In total, five SGLT2 inhibitor trials (31 535 patients, 54% with heart failure) were analysed. Over a median follow-up of 2.2 years, the mean reduction in UA was −0.79 mg/dl (95% confidence interval (CI), −1.03 to −0.54). Every 1 mg/dl reduction in UA was associated with a significantly lower risk of a composite of cardiovascular death and hospitalization for heart failure [hazard ratio, 0.64 (95% CI, 0.46–0.88)] and hospitalization for heart failure (0.68; 95% CI, 0.62–0.74), with a similar risk of mortality. Conclusions: SGLT2 inhibitors reduced UA levels and cardiovascular events independently of heart failure status.