Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease—A Systematic Review and Meta-Analysis
Open accessAbstract
Background: To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Methods: Pubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ2 and I2 statistics. Results: Totally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I2=79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I2=87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients. Conclusions: Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
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A recent systematic review concluded that metformin significantly lowered all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate chronic kidney disease.
“a recent systematic review concluded that metformin significantly lowered all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate chronic kidney disease (163).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [163]
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References 40 · Cited by 39
- Authors
- Hu, Y., Lei, M., Ke, G., Huang, X., Peng, X., Zhong, L., & Fu, P.
- Affiliations
- Sichuan University (CN)
- Chengdu University (CN)
- Corresponding author
- Fu, Ping
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2020-10-07
- Volume
- 11
- Pages
- 559446-559446
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC7575818
- OpenAlex
- W3092536569
- Cited by
- 39
- References
- 40
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, chronic kidney disease, type 2 diabetes, all-cause mortality, cardiovascular events, advanced CKD, drug safety
- MeSH terms
- Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Randomized Controlled Trials as Topic, Renal Insufficiency, Chronic
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