SGLT2 inhibitors, cardiovascular outcomes, and mortality across the spectrum of kidney disease: A systematic review and meta-analysis.

Aims: To evaluate the effects of SGLT2 inhibitors on cardiovascular outcomes and mortality across KDIGO and urinary albumin-to-creatinine ratio [UACR] groups.

Methods: We searched MEDLINE, EMBASE, and CENTRAL up to August 8th, 2023. In pairs, researchers selected large randomized placebo-controlled trials of SGLT2 inhibitors, with minimum duration of one year. Researchers independently extracted study-level data and assessed within-study risk of bias with RoB 2.0 and certainty of evidence with GRADE. Meta-analyses employed a random-effects model.

Results: We included 14 trials, encompassing 97,412 participants and a median follow-up of 2.5 years. Risk of bias was overall low. Overall, SGLT2 inhibitors reduced major adverse cardiovascular events (MACE) (HR 0.89, 95 %-CI 0.85-0.93), cardiovascular death or hospitalization for heart failure (HHF) (HR 0.78, 95 %-CI 0.75-0.82), all-cause death (HR 0.89, 95 %-CI 0.83-0.94), and HHF (HR 0.71, 95 %-CI 0.67-0.75). The effect of SGLT2 inhibitors on MACE was different across KDIGO (P_interaction = 0.038) and UACR (P_interaction = 0.008) groups, with greater benefits in KDIGO Very High (HR 0.72, 95 %-CI 0.61-0.86) and UACR > 300 mg/g (HR 0.76, 95 %-CI 0.68-0.86) groups.

Conclusions: SGLT2 inhibitors are associated with reductions in cardiovascular outcomes and mortality. Greater reductions in MACE are expected in subjects in high-risk groups for kidney disease.