The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: A systematic review and meta-analysis

Background: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM). However, their efficacy in patients with chronic kidney disease (CKD) with or without T2DM has not yet been analyzed. Objective: To assess the cardiovascular and renal effects of SGLT-2 inhibitors in patients with CKD with and without T2DM, including all CKD patients in the current literature. Methods: We searched MEDLINE, EMBASE, CENTRAL and Scopus for randomized controlled trials of SGLT-2 inhibitors that evaluated cardiovascular and kidney outcomes in patients with CKD, or trials in which these patients were a subgroup. We defined 2 primary outcomes: a composite of cardiovascular death or hospitalization for heart failure, and a composite renal outcome. For each outcome, we obtained overall hazard ratios with 95% confidence intervals by using a random effects model. Results: We included 14 randomized controlled trials. SGLT-2 inhibitors decreased the hazard for the primary cardiovascular outcome (HR 0.76; [95% CI 0.72–0.79]) and the primary renal outcome (HR 0.69; [95% CI 0.61–0.79]) in patients with CKD with or without T2DM. We did not find significant differences in the subgroup analyses according to diabetes status, baseline eGFR values or the type of SGLT-2 inhibitor used. Conclusion: In patients with CKD, treatment with SGLT-2 inhibitors in addition to standard therapy conferred protection against cardiovascular and renal outcomes. Further research on patients with non-diabetic CKD should be done to confirm the utility of these medications in this population. (PROSPERO ID: CRD42021275012).