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Meta-Analysis
. 2023 Nov 29;18(11):e0295059.
doi: 10.1371/journal.pone.0295059. eCollection 2023.

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

Carlos Ignacio Reyes-Farias  1 , Marcelo Reategui-Diaz  1 , Franco Romani-Romani  1 , Larry Prokop  2
Affiliations
Meta-Analysis

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

Carlos Ignacio Reyes-Farias et al. PLoS One. .

Abstract

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).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA Flow chart.
*Wrong study design includes articles of rationale and protocols; Wrong population includes articles of studies that analyzed subgroups of the trial sample that were not of interest for our review.
Fig 2
Fig 2. Effects of SGLT-2 inhibitors on the primary outcomes in patients with CKD with or without T2DM.
(A) Primary cardiovascular outcome. (B) Primary renal outcome. Effect estimate calculated with a fixed effects model meta-analysis. CI, confidence interval; HR, hazard ratio; NA, not available.
Fig 3
Fig 3. Effects of SGLT-2 inhibitors on the secondary outcomes in patients with CKD with or without T2DM.
(A) All-cause mortality. (B) MACE. (C) CV death. (D) Hospitalization for HF. Synthetic estimate created with a fixed effects model meta-analysis. CI, confidence interval; HR, hazard ratio; NA, not available.
Fig 4
Fig 4. Effects of SGLT-2 inhibitors on the primary outcomes in patients with CKD according to T2DM status.
(A) Primary cardiovascular outcome. (B) Primary renal outcome. CI, confidence interval; HR, hazard ratio; NA, not available; T2DM, type 2 diabetes mellitus.
Fig 5
Fig 5. Effects of SGLT-2 inhibitors on the secondary outcomes in patients with CKD according to T2DM status.
(A) All-cause mortality. (B) MACE outcome. (C) CV death. (D) Hospitalization for HF. Synthetic estimate created with a fixed effects model meta-analysis. CI, confidence interval; HR, hazard ratio; NA, not available; T2DM, type 2 diabetes mellitus.
See this image and copyright information in PMC

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