Metformin in polycystic ovary syndrome: systematic review and meta-analysis
Open accessAbstract
Objective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome. Design Systematic review and meta-analysis. Data sources Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent. Selection of studies 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence. Main outcome measure Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome. Results Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance. Conclusions Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.
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Two prior systematic reviews of metformin alone versus placebo or no intervention in PCOS found no effect on BMI.
“Two other systematic reviews on metformin alone compared with placebo or no intervention in PCOS, showed no effect on BMI (Lord et al. , 2003; Tang et al. , 2012).”
From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Lord et al. , 2003
Metformin has a near-neutral effect on weight in women with PCOS.
“Metformin has a near-neutral effect on weight, with one meta-analysis finding no effect [164] and others finding small reductions in BMI”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [164]
In other populations, metformin prevents weight gain and appears to assist with weight loss, prevents and manages type 2 diabetes, gestational diabetes, and fatty liver, and reduces cardiovascular disease in type 2 diabetes.
“It is known in other populations to prevent weight gain and appearstoassistwithweightloss,topreventandmanageDM2,gestational diabetes, fatty liver, and reduce cardiovascular disease in DM2 (Lord et al. , 2003; Desilets et al. , 2008; Nestler, 2008; Batra et al. , 2009; NieuwenhuisRuifrok et al. , 2009; Oppelt et al. , 2010; Diabetes Prevention Program Research Group, 2012; Viollet et al. , 2012)”
From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Lord et al., 2003
The Weight section reports no evidence that metformin reduces weight or BMI in women with polycystic ovary syndrome; it does not assess weight effects in other populations. The Possible recommendations section discusses cardiovascular benefit only as a theoretical possibility in that population. Our copy does not establish the claimed effects on type 2 diabetes, gestational diabetes, fatty liver, or cardiovascular disease in other populations. (LLM, conf=0.74)
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- Authors
- Lord, J. M., Flight, I. H. K., & Norman, R. J.
- Affiliations
- Derriford Hospital (GB)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Queen Elizabeth Hospital (AU)
- Corresponding author
- Lord, Jonathan M
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2003-10-23
- Volume
- 327
- Issue
- 7421
- Pages
- 951
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC259161
- OpenAlex
- W2019085069
- Cited by
- 786
- References
- 2
- Citations by year
- 2026: 17 · 2025: 9 · 2024: 13 · 2023: 29 · 2022: 27 · 2021: 16 · 2020: 19 · 2019: 25 · 2018: 30 · 2017: 23 · 2016: 18 · 2015: 30 · 2014: 34 · 2013: 32 · 2012: 29
- FWCI
- 11.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- metformin, polycystic ovary syndrome, ovulation induction, clomiphene citrate, anovulation, pregnancy rate, insulin, metabolic syndrome, blood pressure, LDL cholesterol, gastrointestinal adverse effects, lifestyle intervention
- MeSH terms
- Blood Pressure, Body Weight, Double-Blind Method, Female, Fertility Agents, Female, Humans, Insulin, Lipids, Metformin, Ovulation, Polycystic Ovary Syndrome, Pregnancy, Randomized Controlled Trials as Topic, Single-Blind Method, Treatment Outcome
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