ADIPS Poster Presentation Australasian Diabetes in Pregnancy Society and Society of Obstetric Medicine Australia and New Zealand Joint Scientific Meeting 2025

Metformin for the prevention of adverse outcomes in high-risk pregnancies: an individual participant data meta-analysis of randomised placebo-controlled trials from the Metformin in Pregnancy Study (MiPS) international network (#105)

Aya Mousa 1 , Tait Mason 2 , Tone S Lovvik 3 4 , Sven M Carlsen 3 5 , Yitayeh Belsti 6 , Joanne Enticott 1 , Chau T Tay 1 , Hilkka Nikkinen 7 8 , Laure Morin-Papunen 8 , Kristiina Tertti 9 , Janet Rowam 10 , Jodie Dodd 11 12 , Andrea Deussen 11 , William M Hague 11 , Agnieszka Zawiejska 13 , Rabia Arshad 14 , Jiji E Mathews 15 , Tayyiba Wasim 16 , Magdy A Mohamed 17 , Masoud Mohebbi 18 , Enav Yefet 19 20 , Zohar Nachum 21 22 , Jahanara Ainuddin 23 , Jerrie S Refuerzo 24 , Christy Burden 25 , Jane E Norman 26 , Argyro Syngelaki 27 , Kypros Nicolaides 27 , Hassan Shehata 28 , Eszter Vanky 3 , Helena Teede 1
  1. Monash Centre for Health Research and Implementation, Monash University, Melbourne, VIC, Australia
  2. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, School of Public Health and Preventive Medicine, Melbourne, VIC, Australia
  3. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  4. Department of Obstetrics and Gynecology, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
  5. Department of Internal Medicine, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway
  6. Monash Centre for Health Research and Implementation, Monash University, Melbourne, VIC, Australia
  7. Department of Obstetrics and Gynecology, Medical Research Centre, Oulu University Hospital, Oulu, Finland
  8. University of Oulu, Oulu, Finland
  9. Department of Obstetrics and Gynecology and Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
  10. National Women’s Hospital, Auckland District Health Board, Auckland, New Zealand
  11. Discipline of Obstetrics & Gynaecology and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia
  12. Women's and Babies' Division, Women's & Children's Hospital, North Adelaide, South Australia, Australia
  13. Department of Medical Simulation, Poznan University of Medical Sciences, Poznań, Poland
  14. Department of Pharmacology, Dow University of Health Sciences, Karachi, Pakistan
  15. Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, India
  16. Department of Obstetrics & Gynecology, Services Institute of Medical Sciences, Lahore, Pakistan
  17. Obstetrics & Gynecology Department, Sohag University, Sohag, Egypt
  18. Metabolic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  19. Department of Obstetrics and Gynecology, Tzafon Medical Center, Poriya, Israel
  20. Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
  21. Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
  22. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  23. Department of Obstetrics and Gynecology, Dow University of Health Sciences, Karachi, Pakistan
  24. Maternal-Fetal Medicine Division, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School-UTHealth, Houston, Texas, USA
  25. Faculty of Health Sciences, University of Bristol, Bristol, UK
  26. University of Nottingham, Nottingham, UK
  27. Fetal Medicine Research Institute, King's College Hospital, London, UK
  28. Department of Maternal Medicine, Epsom and St. Helier University Hospitals NHS Trust, Surrey, UK

Background: Metformin is increasingly used in pregnancy despite limited evidence regarding efficacy. We established the Metformin in Pregnancy Study (MiPS) individual participant data (IPD) consortium to determine the effects of metformin on pregnancy outcomes.

Methods: We searched Medline, Embase and all Evidence-based Medicine databases until May 2025, to identify double-blind randomised trials comparing metformin with placebo in high-risk pregnancies. Primary maternal outcomes were gestational diabetes (GDM) and glycaemic indices from oral glucose tolerance tests (OGTTs). Primary neonatal outcomes were gestational age at delivery, neonatal anthropometry, and hypoglycaemia. Multivariable mixed-effects models were adjusted for maternal age, body mass index, gestational age at treatment initiation and baseline blood glucose. 

Findings: Ten trials (n=2695) met inclusion criteria, of which seven provided IPD (n=2482, 92·1%). Following IPD harmonisation, 2297 pregnancies (1159 metformin; 1138 placebo) were included. Metformin did not reduce GDM by any diagnostic criteria; a reduction was only seen in adjusted analysis using IADPSG/ADIPS criteria (13.5% vs 16.7%; adjusted odds ratio [aOR] 0·71; 95% CI 0·52, 0·98). Fasting blood glucose was marginally lower with metformin (mean difference [MD] -0·06 mmol/L; 95% CI -0·11, -0·02), with no difference in two-hour post-OGTT blood glucose. Gestation was longer with metformin (MD 0·29 weeks; 95% CI 0·05, 0·53), corresponding to a lower risk of preterm birth (OR 0·65; 95% CI 0·47, 0·90), and minor increase in neonatal head circumference (MD 2·53 percentile; 95% CI 0·23, 4·83). Metformin reduced gestational weight gain (MD -1·53 kg; 95% CI -2.03, -1.03), with no differences in other maternal or neonatal outcomes.