Metformin to Prevent Late Miscarriage and Preterm Delivery in Women With Polycystic Ovary Syndrome

NCT01587378 | Completed

• 2 other identifiers: 2011/14342011-002203-15
• Study Type: interventional
• Target: 489
• Locations: 3 countries
• Sites: 13

Brief Summary

The overall aim of the PregMet 2 Study is to investigate whether metformin prevents late miscarriages and preterm deliveries in PCOS women treated with metformin from first trimester of pregnancy to delivery in a large, randomized, controlled, multi-centre trial setting. The investigators hypothesis is that metformin compared to placebo treatment from the first trimester to term, reduces the prevalence of late miscarriage (gestational week 13-22) and preterm birth (gestational week \< 37) in PCOS women diagnosed according to Rotterdam 2003 consensus criteria, with singleton pregnancy.

Conditions

Pregnancy; Polycystic Ovary Syndrome

Keywords

miscarriage; preterm birth; prevention

Outcome Measures

Primary Outcomes (1)

• combined incidence of late miscarriages and preterm births

  This includes spontaneous births, induced vaginal deliveries and operative deliveries on medical indications.

  at delivery

Secondary Outcomes (6)

• NICU admissions and total number of days in NICU/baby

  2 months

• number of patients hospitalized

  at delivery

• Total number of hospitalization days/ hospitalized participant

  2 months

• Prevalence of gestational diabetes

  up to delivery

• Prevalence of preeclampsia

  up to delivery

Study Arms (2)

metformin

EXPERIMENTAL

Drug: Metformin

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

Metformin DRUG

Metformin 500 mg tablets, 1 tablet x 2 daily the first week and then 2 tablets x 2 daily from the second week to delivery

metformin

placebo DRUG

identical placebo tablets, 1 tablet x 2 daily the first week and then 2 tablets x 2 daily from the second week to delivery

placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-45 years
• Mode of conception: Any
• Single, viable fetus, diagnosed by vaginal ultrasound
• Wash out for metformin: at least 7 days
• Able to communicate fluently in the official language at the study cite or English

You may not qualify if:

• Any type of diabetes (except GDM in former pregnancy)
• Known liver disease or ALAT \> 100 IU/L
• Known kidney disease or creatinine \> 110 μmol/L
• Known alcohol or drug abuse
• Use of drugs interfering with metformin: erytromycin (or other macrolides), cimetidine, anticoagulation therapy
• Unsuitable for participation of other reasons

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• Vestre Viken Hospital Trust: collaborator
• Landspitali University Hospital: collaborator
• Uppsala University Hospital: collaborator
• Haukeland University Hospital: collaborator
• Karolinska University Hospital: collaborator
• St. Olavs Hospital: collaborator
• Sykehuset Telemark: collaborator
• Alesund Hospital: collaborator
• The Hospital of Vestfold: collaborator
• Nordlandssykehuset HF: collaborator
• Norrlands universitetssjukhus Umeå: collaborator
• Sykehuset Innlandet HF: collaborator
• Vestre Viken Ringerike Sykehus: collaborator

Study Sites (13)

Landspital University Hospital

Reykjavik, 101, Iceland

Location

Sykehuset Ålesund

Ålesund, 6026, Norway

Location

Haukeland University Hospital

Bergen, 5000, Norway

Location

Nordlandssykehuset HF

Bodø, 1480, Norway

Location

Sykehuset Innlandet

Brumunddal, 2380, Norway

Location

Vestre Viken Hospital Trust

Drammen, Norway

Location

Vestre Viken Ringerike sykehus

Hønefoss, 3511, Norway

Location

Sykehuset Telemark

Skien, 3710, Norway

Location

St Olavs Hospital

Trondheim, 7006, Norway

Location

Sentralsykehuset i Vestfold

Tønsberg, 3116, Norway

Location

Karolinska Universitetssjukhus

Stockholm, 17176, Sweden

Location

Norrlands universitetssjukhus

Umeå, 901 85, Sweden

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (5)

• Lovvik TS, Carlsen SM, Salvesen O, Steffensen B, Bixo M, Gomez-Real F, Lonnebotn M, Hestvold KV, Zabielska R, Hirschberg AL, Trouva A, Thorarinsdottir S, Hjelle S, Berg AH, Andrae F, Poromaa IS, Mohlin J, Underdal M, Vanky E. Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 Apr;7(4):256-266. doi: 10.1016/S2213-8587(19)30002-6. Epub 2019 Feb 18.

  PMID: 30792154 RESULT

• Ryssdal M, Skage JE, Jarmund AH, Hanem LGE, Lovvik TS, Giskeodegard GF, Iversen AC, Vanky E. Metformin Treatment in PCOS Pregnancies Reduces Maternal Infections and Increases the Risk of Allergies and Eczema in the Offspring: Post Hoc Analyses of Two Randomised Controlled Trials and One Follow-Up Study. BJOG. 2025 Nov;132(12):1823-1832. doi: 10.1111/1471-0528.18320. Epub 2025 Aug 11.

  PMID: 40785326 DERIVED

• Nordtvedt E, Kessler J, Ebbing C, Acharya G, Lovvik TS, Salvesen KA, Salvesen O, Vanky E, Kahrs BH. Placental and cerebral circulation in fetuses of mothers with polycystic ovary syndrome and the effect of Metformin exposure. BMC Pregnancy Childbirth. 2025 Jul 10;25(1):749. doi: 10.1186/s12884-025-07866-9.

  PMID: 40640743 DERIVED

• Husby AE, Simpson MR, Dalbye R, Larsen M, Vanky E, Lovvik TS. Childbirth experiences in women with polycystic ovary syndrome: A cohort study. Acta Obstet Gynecol Scand. 2024 Jun;103(6):1092-1100. doi: 10.1111/aogs.14800. Epub 2024 Feb 17.

  PMID: 38366810 DERIVED

• Stokkeland LMT, Giskeodegard GF, Ryssdal M, Jarmund AH, Steinkjer B, Madssen TS, Stafne SN, Stridsklev S, Lovvik TS, Iversen AC, Vanky E. Changes in Serum Cytokines Throughout Pregnancy in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2022 Jan 1;107(1):39-52. doi: 10.1210/clinem/dgab684.

  PMID: 34529073 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Abortion, Spontaneous; Premature Birth

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Eszter I Vanky, md phd

  Norwegian University of Science and Technology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: April 30, 2012
• Study Start: October 1, 2012
• Primary Completion: October 31, 2017
• Study Completion: October 31, 2017
• Last Updated: February 26, 2019

Record last verified: 2019-02

Locations

SE (3); IC (1); NO (9)