University of Oulu

Johanna Melin, Maria Forslund, Simon Alesi, Terhi Piltonen, Daniela Romualdi, Poli Mara Spritzer, Chau Thien Tay, Alexia Pena, Selma Feldman Witchel, Aya Mousa, Helena Teede, The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials, European Journal of Endocrinology, Volume 189, Issue 2, August 2023, Pages S38–S64,

The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome : a systematic review and meta-analysis of randomized controlled trials

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Author: Melin, Johanna1,2; Forslund, Maria1,3; Alesi, Simon1;
Organizations: 1Monash Centre for Health Research and Implementation, School of public Health and Preventive Medicine, Monash University, Clayton, VIC 3168, Australia
2Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, 00014 Helsinki, Finland
3Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
4Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine and Medical Research Centre, Oulu University Hospital, University of Oulu, 90014 Oulu, Finland
5Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
6Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazi
7Discipline of Paediatics, The University of Adelaide and Robinson Research Institute, Adelaide, South Australia 5005, Australia
8Division of Pediatric Endocrinology, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
9Endocrine and Diabetes Units, Monash Health, Clayton, VIC 3169, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5 MB)
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Language: English
Published: Bioscientifica, 2023
Publish Date: 2023-10-20


Objective: Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps remain regarding its efficacy and the specific outcomes in this population. This review evaluates the effectiveness of metformin and lifestyle modification compared with placebo in the management of PCOS and will inform the forthcoming, 2023 evidence-based PCOS guidelines.

Design: Systematic review and meta-analysis of the literature.

Methods: A search was performed in MEDLINE, EMBASE, PsycINFO, All EBM, and CINAHL. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomized controlled trials published in English through July 2022.

Results: Moderate certainty of evidence showed a larger reduction of body mass index (BMI) (mean difference [MD] −0.53, 95% confidence interval [CI] −0.95 to −0.12 kg/m2), homeostatic model assessment for insulin resistance (MD −0.50, 95% CI −0.91 to −0.09) (critical outcomes), and fasting glucose (MD −0.13, 95% CI −0.19 to −0.07 mmol/L) with metformin compared to placebo with increased mild gastrointestinal adverse effects (odds ratio [OR] 7.67, 95% CI 2.74–21.46). Low certainty of evidence showed a larger reduction of waist–hip ratio (MD −0.02, 95% CI −0.03 to −0.00), total cholesterol (MD −0.24, 95% CI −0.43 to −0.05 mmol/L), low-density lipoprotein (MD −0.16, 95% CI −0.30 to −0.01 mmol/L), and triglycerides (MD −0.11, 95% CI −0.20 to −0.02 mmol/L) with metformin than placebo.

Conclusions: Metformin should be considered an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance, and lipids.

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Series: European journal of endocrinology
ISSN: 0804-4643
ISSN-E: 1479-683X
ISSN-L: 0804-4643
Volume: 189
Issue: 2
Pages: S37 - S63
DOI: 10.1093/ejendo/lvad098
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3123 Gynaecology and paediatrics
Funding: J.M. received funding from Finska Läkaresällskapet and Orionin Tutkimussäätiö. M.F. received funding from the Iris foundation and Stiftelsen Handlanden Hjalmar Svenssons. A.M. and H.T. are supported by research fellowships from the National Health and Medical Research Council (NHMRC) of Australia. C.T.T. is supported by the Royal Australasian College of Physicians Foundation Roger Bartop Research Establishment Fellowship.
Dataset Reference: The data underlying this article is secondary, aggregated from already published work.
Copyright information: © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.