Metformin in Pregnant PCOS Women

NCT00159536 | Completed Phase 3

• 1 other identifier: PregMet
• Study Type: interventional
• Target: 257
• Locations: 1 country
• Sites: 10

Brief Summary

To investigate the effect of metformin on pregnancy complications and pregnancy outcome in the II. and III. trimester of pregnancy in women with polycystic ovary syndrome.

Conditions

Polycystic Ovary Syndrome

Keywords

PCOS; metformin; pregnancy; preeclampsia; diabetes; preterm delivery

Outcome Measures

Primary Outcomes (4)

• Gestational diabetes

  up to delivery

• incidence of metabolic syndrome and neurophysiologic parameters in offspring

  Within 18 years

• Preterm delivery

  up to delivery

• pre-eclampsia

  up to delivery

Secondary Outcomes (7)

• emesis and hyperemesis

  up to delivery

• Breastfeeding

  One year post partum

• weight change

  up to delivery

• blood pressure change

  up to delivery

• Incident of instrumental deliveries

  at delivery

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 1000mg x 2 daily

Drug: Metformin

placebo

PLACEBO COMPARATOR

Placebo x 2 daily

Drug: Placebo

Interventions

Metformin DRUG

Metformin 1000 mg x 2 per day. Orally. From inclusion (before gestational week 12) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study

Also known as: metformin from Weifa 500 mg / tablet

Metformin

Placebo DRUG

Placebo, 2 tablets x 2 daily.Orally. From inclusion (that is before gestational week 12) to delivery. Verbal and written diet and lifestyle advices at inclusion to the study

Also known as: Placebo from Weifa

placebo

Eligibility Criteria

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

You may qualify if:

• years,
• PCOS diagnosis according to Rotterdam criteria
• single, viable, ultrasound verified fetus
• if metformin was used at conception and early pregnancy, at least 7 days of "wash out"

You may not qualify if:

• known liver disease or ALAT \> 90 nmol/L
• known renal disease or creatinine \> 110 micromol/L
• diabetes mellitus
• alcohol or drug abuse
• peroral steroid treatment
• not suitable for other reasons

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator

Study Sites (10)

Ålesund Hospital

Ålesund, Norway

Location

University hospital of Bergen

Bergen, Norway

Location

Central Hospital of Northern Norway

Bodø, Norway

Location

Buskerud Hospital

Drammen, Norway

Location

Haugesund Hospital

Haugesund, Norway

Location

Ringerike Hospital

Hønefoss, Norway

Location

Elvebredden Gynekologpraksis

Kristiansand, Norway

Location

Lillehammer Hospital

Lillehammer, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

Departments of Obstetrics and Gynecology and Endocrinology, St. Olav's Hospital

Trondheim, Norway

Location

Related Publications (18)

• Underdal MO, Stridsklev S, Oppen IH, Hogetveit K, Andersen MS, Vanky E. Does Metformin Treatment During Pregnancy Modify the Future Metabolic Profile in Women With PCOS? J Clin Endocrinol Metab. 2018 Jun 1;103(6):2408-2413. doi: 10.1210/jc.2018-00485.

  PMID: 29659896 BACKGROUND

• Vanky E, Stridsklev S, Heimstad R, Romundstad P, Skogoy K, Kleggetveit O, Hjelle S, von Brandis P, Eikeland T, Flo K, Berg KF, Bunford G, Lund A, Bjerke C, Almas I, Berg AH, Danielson A, Lahmami G, Carlsen SM. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010 Dec;95(12):E448-55. doi: 10.1210/jc.2010-0853. Epub 2010 Oct 6.

  PMID: 20926533 RESULT

• Vanky E, Carlsen SM. Androgens and antimullerian hormone in mothers with polycystic ovary syndrome and their newborns. Fertil Steril. 2012 Feb;97(2):509-15. doi: 10.1016/j.fertnstert.2011.11.021. Epub 2011 Dec 10.

  PMID: 22154766 RESULT

• Shetelig Lovvik T, Stridsklev S, Carlsen SM, Salvesen O, Vanky E. Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect? J Clin Endocrinol Metab. 2016 Jun;101(6):2325-31. doi: 10.1210/jc.2015-3498. Epub 2016 Feb 2.

  PMID: 26835542 RESULT

• Hanem LGE, Stridsklev S, Juliusson PB, Salvesen O, Roelants M, Carlsen SM, Odegard R, Vanky E. Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1612-1621. doi: 10.1210/jc.2017-02419.

  PMID: 29490031 RESULT

• Hanem LGE, Salvesen O, Juliusson PB, Carlsen SM, Nossum MCF, Vaage MO, Odegard R, Vanky E. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial. Lancet Child Adolesc Health. 2019 Mar;3(3):166-174. doi: 10.1016/S2352-4642(18)30385-7. Epub 2019 Jan 29.

  PMID: 30704873 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

• Ujvari D, Trouva A, Hirschberg AL, Vanky E. Maternal serum levels of prokineticin-1 related to pregnancy complications and metformin use in women with polycystic ovary syndrome: a post hoc analysis of two prospective, randomised, placebo-controlled trials. BMJ Open. 2023 Nov 21;13(11):e073619. doi: 10.1136/bmjopen-2023-073619.

  PMID: 37989369 DERIVED

• Trouva A, Alvarsson M, Calissendorff J, Asvold BO, Vanky E, Hirschberg AL. Thyroid Status During Pregnancy in Women With Polycystic Ovary Syndrome and the Effect of Metformin. Front Endocrinol (Lausanne). 2022 Feb 21;13:772801. doi: 10.3389/fendo.2022.772801. eCollection 2022.

  PMID: 35265033 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

• Andrae F, Abbott D, Stridsklev S, Schmedes AV, Odsaeter IH, Vanky E, Salvesen O. Sustained Maternal Hyperandrogenism During PCOS Pregnancy Reduced by Metformin in Non-obese Women Carrying a Male Fetus. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3762-70. doi: 10.1210/clinem/dgaa605.

  PMID: 32866967 DERIVED

• Greger HK, Hanem LGE, Ostgard HF, Vanky E. Cognitive function in metformin exposed children, born to mothers with PCOS - follow-up of an RCT. BMC Pediatr. 2020 Feb 10;20(1):60. doi: 10.1186/s12887-020-1960-2.

  PMID: 32039724 DERIVED

• Underdal MO, Salvesen O, Henriksen AH, Andersen M, Vanky E. Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz053. doi: 10.1210/clinem/dgz053.

  PMID: 31613965 DERIVED

• Stridsklev S, Salvesen O, Salvesen KA, Carlsen SM, Vanky E. Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy Controls. Int J Endocrinol. 2018 Aug 16;2018:2604064. doi: 10.1155/2018/2604064. eCollection 2018.

  PMID: 30186323 DERIVED

• Hjorth-Hansen A, Salvesen O, Engen Hanem LG, Eggebo T, Salvesen KA, Vanky E, Odegard R. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS. J Clin Endocrinol Metab. 2018 Feb 1;103(2):740-747. doi: 10.1210/jc.2017-01191.

  PMID: 29165598 DERIVED

• Christiansen SC, Vanky E, Klungland H, Stafne SN, Morkved S, Salvesen KA, Saether M, Carlsen SM. The effect of exercise and metformin treatment on circulating free DNA in pregnancy. Placenta. 2014 Dec;35(12):989-93. doi: 10.1016/j.placenta.2014.09.010. Epub 2014 Sep 23.

  PMID: 25282112 DERIVED

• Helseth R, Vanky E, Stridsklev S, Vogt C, Carlsen SM. Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin. Eur J Endocrinol. 2014 Apr 10;170(5):769-75. doi: 10.1530/EJE-13-0859. Print 2014 May.

  PMID: 24595965 DERIVED

• Carlsen SM, Martinussen MP, Vanky E. Metformin's effect on first-year weight gain: a follow-up study. Pediatrics. 2012 Nov;130(5):e1222-6. doi: 10.1542/peds.2012-0346. Epub 2012 Oct 15.

  PMID: 23071212 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Pre-Eclampsia; Diabetes Mellitus; Premature Birth

Interventions

Metformin; Tablets

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; Hypertension, Pregnancy-Induced; Pregnancy Complications; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Eszter I Vanky, MD, PhD

  Norwegian University of Science and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: September 8, 2005
• First Posted: September 12, 2005
• Study Start: February 1, 2005
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

NO (10)