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Cited by 99Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesHeart Failure Treatment and Management

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

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Mavrakanas, Thomas A., Tsoukas, Michael A., Brophy, James M., Sharma, Abhinav, Gariani, Karim·2023·Scientific Reports
DOI 10.1038/s41598-023-42989-zPMC PMC10517929

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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/1.73m 2 (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/1.73m 2 ). 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.

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Cited by

Sorted by citations

Authors
Mavrakanas, T. A., Tsoukas, M. A., Brophy, J. M., Sharma, A., & Gariani, K.
Affiliations
  • McGill University Health Centre (CA)
  • University Hospital of Geneva (CH)
Corresponding author
Mavrakanas, Thomas A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-09-23
Volume
13
Issue
1
Pages
15922-15922
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-42989-z
PMC
PMC10517929
OpenAlex
W4386987092
Cited by
99
References
14
Citations by year
2026: 37 · 2025: 39 · 2024: 22 · 2023: 1
FWCI
3.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by)
Funders
  • the Fonds de Recherche Santé Quebec
  • Quebec Society of Nephrology
  • Alberta Innovates Health Solution
  • European Society of Cardiology young investigator grant
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
SGLT2 inhibitors, chronic kidney disease, cardiovascular outcomes, renal outcomes, cardiovascular mortality, heart failure hospitalization, chronic kidney disease progression, acute kidney injury, treatment discontinuation, estimated glomerular filtration rate, diabetes mellitus, major adverse cardiovascular events, all-cause mortality, drug safety in kidney disease, drug dosing in kidney disease
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Heart Failure, Humans, Kidney, Renal Insufficiency, Chronic, Acute Kidney Injury

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