Lange Neuen, B; Young, T; Heerspink, H; Neal, B; Perkovic, V; Billot, L; Mahaffey, KW; ... Jardine, MJ; + view all Lange Neuen, B; Young, T; Heerspink, H; Neal, B; Perkovic, V; Billot, L; Mahaffey, KW; Charytan, DM; Wheeler, DC; Arnott, C; Bompoint, S; Levin, A; Jardine, MJ; - view fewer (2019) SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. The Lancet Diabetes and Endocrinology , 7 (11) pp. 845-854. 10.1016/S2213-8587(19)30256-6.

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Abstract

Background The impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on kidney failure, particularly the need for dialysis and transplantation, or death due to kidney disease, has been uncertain. Methods We conducted a systematic review and meta-analysis of randomized, controlled, cardiovascular or kidney outcome trials of SGLT2 inhibitors reporting effects on kidney failure and other major kidney outcomes in people with type 2 diabetes (PROSPERO registration number CRD42019131774). MEDLINE and EMBASE were searched from inception to 1 March 2019 to identify eligible trials. The primary outcome was kidney failure, defined as dialysis, transplantation, or death due to kidney disease. We used random effects models to obtain summary relative risks (RR) with 95% confidence intervals (CI) and random effects meta-regression to explore effect modification by baseline estimated glomerular filtration rate (eGFR). Findings Data were obtained from four studies including 38,723 participants of whom 218 reached kidney failure, 310 developed end-stage kidney disease (ESKD), and 943 experienced acute kidney injury (AKI). SGLT2 inhibitors reduced the risk of kidney failure by 29% (RR 0 71, 95% CI 0 54-0 93, p=0 014), ESKD by 32% (RR 0 68, 95% CI 0 55-0 85, p=0 001), and AKI by 25% (RR 0 75, 95% CI 0 66-0 85, p<0 0001), with consistent benefits across studies. While there was some evidence that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function (P-trend=0 07), there was clear, separate evidence of benefit for all eGFR subgroups, including for participants with baseline eGFR <45 mL/min/1 73m2 (RR 0 70, 95% CI 0 54-0 91, p=0 008). Interpretation SGLT2 inhibitors reduce the risk of kidney failure and provide protection against acute kidney injury. These data provide substantive evidence supporting the use of SGLT2 inhibitors to prevent major kidney outcomes in people with type 2 diabetes.

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