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

Xue Li; Stefano Celotto; Damiano Pizzol; Danijela Gasevic; Meng Meng Ji; Tommaso Barnini; Marco Solmi; Brendon Stubbs; Lee Smith; Guillermo F. López Sánchez; Gabriella Pesolillo; Zengli Yu; Ioanna Tzoulaki; Evropi Theodoratou; John P.A. Ioannidis; Nicola Veronese; Jacopo Demurtas

doi:10.1111/eci.13536

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

Xue Li^*, Stefano Celotto, Damiano Pizzol, Danijela Gasevic, Meng Meng Ji, Tommaso Barnini, Marco Solmi, Brendon Stubbs, Lee Smith, Guillermo F. López Sánchez, Gabriella Pesolillo, Zengli Yu, Ioanna Tzoulaki, Evropi Theodoratou, John P.A. Ioannidis, Nicola Veronese, Jacopo Demurtas

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

19 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e13536
Journal	European Journal of Clinical Investigation
Volume	51
Issue number	7
DOIs	https://doi.org/10.1111/eci.13536
Publication status	Published - Jul 2021

Keywords

GRADE
meta-analysis
metformin
umbrella

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/eci.13536

Cite this

Li, X., Celotto, S., Pizzol, D., Gasevic, D., Ji, M. M., Barnini, T., Solmi, M., Stubbs, B., Smith, L., López Sánchez, G. F., Pesolillo, G., Yu, Z., Tzoulaki, I., Theodoratou, E., Ioannidis, J. P. A., Veronese, N., & Demurtas, J. (2021). Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses. European Journal of Clinical Investigation, 51(7), Article e13536. https://doi.org/10.1111/eci.13536

@article{e979e0a565e64a0794a93882191f71d8,

title = "Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses",

abstract = "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.",

keywords = "GRADE, meta-analysis, metformin, umbrella",

author = "Xue Li and Stefano Celotto and Damiano Pizzol and Danijela Gasevic and Ji, {Meng Meng} and Tommaso Barnini and Marco Solmi and Brendon Stubbs and Lee Smith and {L{\'o}pez S{\'a}nchez}, {Guillermo F.} and Gabriella Pesolillo and Zengli Yu and Ioanna Tzoulaki and Evropi Theodoratou and Ioannidis, {John P.A.} and Nicola Veronese and Jacopo Demurtas",

note = "Publisher Copyright: {\textcopyright} 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jul,

doi = "10.1111/eci.13536",

language = "English",

volume = "51",

journal = "European Journal of Clinical Investigation",

issn = "0014-2972",

publisher = "Wiley-Blackwell",

number = "7",

}

Li, X, Celotto, S, Pizzol, D, Gasevic, D, Ji, MM, Barnini, T, Solmi, M, Stubbs, B, Smith, L, López Sánchez, GF, Pesolillo, G, Yu, Z, Tzoulaki, I, Theodoratou, E, Ioannidis, JPA, Veronese, N & Demurtas, J 2021, 'Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses', European Journal of Clinical Investigation, vol. 51, no. 7, e13536. https://doi.org/10.1111/eci.13536

TY - JOUR

T1 - Metformin and health outcomes

T2 - An umbrella review of systematic reviews with meta-analyses

AU - Li, Xue

AU - Celotto, Stefano

AU - Pizzol, Damiano

AU - Gasevic, Danijela

AU - Ji, Meng Meng

AU - Barnini, Tommaso

AU - Solmi, Marco

AU - Stubbs, Brendon

AU - Smith, Lee

AU - López Sánchez, Guillermo F.

AU - Pesolillo, Gabriella

AU - Yu, Zengli

AU - Tzoulaki, Ioanna

AU - Theodoratou, Evropi

AU - Ioannidis, John P.A.

AU - Veronese, Nicola

AU - Demurtas, Jacopo

N1 - Publisher Copyright: © 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

KW - GRADE

KW - meta-analysis

KW - metformin

KW - umbrella

UR - http://www.scopus.com/inward/record.url?scp=85102530537&partnerID=8YFLogxK

U2 - 10.1111/eci.13536

DO - 10.1111/eci.13536

M3 - Review article

AN - SCOPUS:85102530537

SN - 0014-2972

VL - 51

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

IS - 7

M1 - e13536

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this