Metformin and health outcomes: an umbrella review of systematic reviews with meta-analyses

Li, Xue and Celotto, Stefano and Pizzol, Damiano and Gasevic, Danijela and Ji, Meng-Meng and Barnini, Tommaso and Solmi, Marco and Stubbs, Brendon and Smith, Lee and López Sánchez, Guillermo F. and Pesolillo, Gabriella and Yu, Zengli and Tzoulaki, Ioanna and Theodoratou, Evropi and Ioannidis, John P. A. and Veronese, Nicola and Demurtas, Jacopo (2021) Metformin and health outcomes: an umbrella review of systematic reviews with meta-analyses. European Journal of Clinical Investigation. ISSN 1365-2362

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Background: The objective was to capture the breadth of outcomes that have been associated with metformin use and to systematically assess the quality, strength and credibility of these associations using the umbrella review methodology. Methods: Four major databases were searched until 31 May 2020. Meta‐analyses of observational studies and meta‐analyses of randomized controlled trials (RCTs) (including active and placebo control arms) were included. Results: From 175 eligible publications, we identified 427 different meta‐analyses, including 167 meta‐analyses of observational studies, 147 meta‐analyses of RCTs for metformin vs placebo/no treatment and 113 meta‐analyses of RCTs for metformin vs active medications. There was no association classified as convincing or highly suggestive from meta‐analyses of observational studies, but some suggestive/weak associations of metformin use with a lower mortality risk of CVD and cancer. In meta‐analyses of RCTs, metformin was associated with a lower incidence of diabetes in people with prediabetes or no diabetes at baseline; lower ovarian hyperstimulation syndrome incidence (in women in controlled ovarian stimulation); higher success for clinical pregnancy rate in poly‐cystic ovary syndrome (PCOS); and significant reduction in body mass index in people with type 1 diabetes mellitus, in women who have obesity/overweight with PCOS and in obese/overweight women. Of 175 publications, 166 scored as low or critically low quality per AMSTAR 2 criteria. Conclusions: Observational evidence on metformin seems largely unreliable. Randomized evidence shows benefits for preventing diabetes and in some gynaecological and obstetrical settings. However, almost all meta‐analyses are of low or critically low quality according to AMSTAR 2 criteria.

Item Type: Journal Article
Keywords: Metformin, Umbrella Review, Health Outcomes, GRADE, meta‐analysis
Faculty: Faculty of Health, Education, Medicine & Social Care
Faculty of Science & Engineering
SWORD Depositor: Symplectic User
Depositing User: Symplectic User
Date Deposited: 03 Mar 2021 15:33
Last Modified: 16 Mar 2021 17:14

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