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

by Carlos Ignacio Reyes-Farias, Marcelo Reategui-Diaz, Franco Romani-Romani, Larry Prokop

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).