University of Oulu

Mousa A, Løvvik T, Hilkka I, et al, Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis, BMJ Open 2020;10:e036981. doi: 10.1136/bmjopen-2020-036981

Metformin in Pregnancy Study (MiPS) : protocol for a systematic review with individual patient data meta-analysis

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Author: Mousa, Aya1; Løvvik, Tone2; Ijäs, Hilkka3;
Organizations: 1Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
2Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
3Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Centre, PEDEGO Research Unit, Oulu, Finland
4Department of Endocrinology, St Olavs Hospital, Trondheim, Norway
5Department of Obstetrics and Gynecology, University of Turku, Turku, Finland
6Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland
7Department of Medicine, University of Turku, Turku, Finland
8Fetal Medicine Research Unit, King's College London, London, UK
9Department of Maternal Medicine, Epsom Hospital, Epsom and St Helier University Hospitals NHS Trust, Epsom, Surrey, UK
10Faculty of Health Sciences, University of Bristol, Bristol, UK
11Auckland District Health Board, Auckland, New Zealand
12School of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
13Robinson Research Institute, The University of Adelaide Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia
14Women's and Babies Division, Women's and Children's Hospital, Adelaide, North Adelaide, South Australia, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: BMJ, 2020
Publish Date: 2020-07-07


Introduction: Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.

Methods and analysis: MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.

Ethics and dissemination: All IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

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Series: BMJ open
ISSN: 2044-6055
ISSN-E: 2044-6055
ISSN-L: 2044-6055
Volume: 10
Issue: 5
Article number: e036981
DOI: 10.1136/bmjopen-2020-036981
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
317 Pharmacy
3121 General medicine, internal medicine and other clinical medicine
Funding: AM is supported by a Peter Doherty Biomedical Research Fellowship provided by the National Health and Medical Research Council (NHMRC) of Australia. HJT is supported by a Senior Research Fellowship from the NHMRC.
Copyright information: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: