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Cited by 21Diabetes Treatment and ManagementMetabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and Lipoproteins

Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis

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Bahardoust, Mansour, Mousavi, Sepideh, Yariali, Mohsen, Haghmoradi, Meisam, Hadaegh, Farzad, Khalili, Davood, Delpisheh, Ali·2023·Journal of Diabetes & Metabolic Disorders
DOI 10.1007/s40200-023-01309-yPMC PMC11196519
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Abstract

Purpose The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients. Methods PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785). Summary This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making. Supplementary information The online version contains supplementary material available at 10.1007/s40200-023-01309-y.

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  • Metformin is inexpensive and widely available.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]

    The Introduction describes metformin as low cost, supporting “inexpensive.” It also calls metformin widely used and a first-line treatment, but does not establish that it is widely available. Page numbers were not provided in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Metformin reduces risk of microvascular complications.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]

    The Introduction (page unavailable) reports that metformin may provide renal protection and decrease the risk of diabetes complications compared with conventional treatment. Renal complications are one type of microvascular complication, but the paper does not establish a reduction in microvascular complications generally; its own analysis addresses cardiovascular events and mortality. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Metformin is effective and safe.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]

    The Introduction describes metformin as glucose-lowering and having a low risk of hypoglycemia, supporting effectiveness and one aspect of safety. It does not establish the broader, unqualified claim that metformin is safe. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Metformin reduces risk of cardiovascular events.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]

  • Metformin reduces risk of death.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]

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Research works printed but not linked: 26

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Authors
Bahardoust, M., Mousavi, S., Yariali, M., Haghmoradi, M., Hadaegh, F., Khalili, D., & Delpisheh, A.
Affiliations
  • Shahid Beheshti University (IR)
  • Tabriz University of Medical Sciences (IR)
  • Kashan University of Medical Sciences (IR)
  • Urmia University (IR)
  • Research Institute for Endocrine Sciences (IR)
Corresponding author
  • Khalili, Davood
  • Delpisheh, Ali
ORCID
Venue
Journal of Diabetes & Metabolic Disorders
Publisher
Springer Science and Business Media LLC
Published
2023-10-11
Volume
23
Issue
1
Pages
27-38
ISSN
2251-6581 (ISSN-L)
DOI
10.1007/s40200-023-01309-y
PMC
PMC11196519
OpenAlex
W4387530062
Cited by
21
References
4
Citations by year
2026: 5 · 2025: 13 · 2024: 3
FWCI
0.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes & Metabolic Disorders (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
metformin, diabetes mellitus, all-cause mortality, cardiovascular mortality, cardiovascular disease incidence, sulfonylureas, antidiabetic drugs, placebo comparison, cardiovascular risk

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