Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Sep 23;13(1):15922.
doi: 10.1038/s41598-023-42989-z.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis

Thomas A Mavrakanas  1 , Michael A Tsoukas  2 , James M Brophy  3 , Abhinav Sharma  3 , Karim Gariani  4
Affiliations
Meta-Analysis

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis

Thomas A Mavrakanas et al. Sci Rep. .

Abstract

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

PubMed Disclaimer

Conflict of interest statement

Dr. Mavrakanas received speaker honoraria from Daiichi Sankyo, BMS Canada, Janssen, Astra Zeneca, and Pfizer and has served on advisory boards for Boehringer Ingelheim, Bayer, GSK, and Servier outside the submitted work. He has also received an unrestricted research grant from Astra Zeneca. Dr. Tsoukas received speaker honoraria from NovoNordisk, Boehringer-Ingelheim, Janssen, Eli Lilly, and AstraZeneca outside the submitted work. Dr. Sharma received research and personal support from Roche Diagnostics, Boehringer-Ingelheim, Servier, Novartis, AstraZeneca, Janssen, Novo-Nordisk, BMS-Pfizer, and Takeda. The remaining authors have nothing to disclose.

Figures

Figure 1
Figure 1
Forest plot showing the incidence of cardiovascular death with SGLT-2 inhibitors compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95% CI). A lower incidence of cardiovascular death is identified with SGLT-2 inhibitors compared with placebo in patients with and without CKD (p for interaction 0.72). A random effects model is used.
Figure 2
Figure 2
Forest plot showing the incidence of heart failure with SGLT-2 inhibitors compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95% CI). A lower incidence of heart failure is identified with SGLT-2 inhibitors compared with placebo in patients with and without CKD (p for interaction 0.08 suggesting a stronger treatment effect with SGLT-2 inhibitors in the subgroup of patients with CKD). A random effects model is used.
Figure 3
Figure 3
Forest plot showing the incidence of major adverse cardiovascular events (MACE) with SGLT-2 inhibitors compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95% CI). A lower incidence of MACE is identified with SGLT-2 inhibitors compared with placebo in patients with and without CKD (p for interaction 0.44). A random effects model is used. Definition of MACE is detailed in Table 1.
Figure 4
Figure 4
Forest plot showing the incidence of the composite renal outcome with SGLT-2 inhibitors compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95% CI). A lower incidence of the composite renal outcome is identified with SGLT-2 inhibitors compared with placebo in patients with and without CKD (p for interaction 0.30). A random effects model is used. Definition of the composite renal outcome is detailed in Table 1.
Figure 5
Figure 5
Forest plot showing the incidence of the acute kidney injury with SGLT-2 inhibitors compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95% CI). A lower incidence of the acute kidney injury is identified with SGLT-2 inhibitors compared with placebo in patients with CKD. A random effects model is used.
See this image and copyright information in PMC

References

    1. Alicic RZ, Johnson EJ, Tuttle KR. SGLT2 inhibition for the prevention and treatment of diabetic kidney disease: A review. Am. J. Kidney Dis. 2018;72(2):267–277. doi: 10.1053/j.ajkd.2018.03.022. - DOI - PubMed
    1. Cowie MR, Fisher M. SGLT2 inhibitors: Mechanisms of cardiovascular benefit beyond glycaemic control. Nat. Rev. Cardiol. 2020;17(12):761–772. doi: 10.1038/s41569-020-0406-8. - DOI - PubMed
    1. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 2020;383(15):1436–1446. doi: 10.1056/NEJMoa2024816. - DOI - PubMed
    1. Solomon J, Festa MC, Chatzizisis YS, Samanta R, Suri RS, Mavrakanas TA. Sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease. Pharmacol. Ther. 2022;10(242):108330. - PubMed
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J. Clin. Epidemiol. 2009;62(10):1006–1012. doi: 10.1016/j.jclinepi.2009.06.005. - DOI - PubMed

Publication types

MeSH terms

Substances