RecruitingPhase 3NCT02947503

Pregnancy Outcomes: Effects of Metformin Study (POEM Study)

Pregnancy Outcomes: Effects of Metformin Study (POEM Study), a Long Term Randomized Controlled Study in Gestational Diabetes


Sponsor

Bethesda Diabetes Research Center

Enrollment

500 participants

Start Date

Nov 26, 2019

Study Type

INTERVENTIONAL

Conditions

Summary

One approach to prevent the rising burden of diabetes is to address the issue of gestational diabetes mellitus (GDM). GDM has a growing prevalence up to 5-10% (and even higher in specific subgroups), with a pregnant population becoming older and more obese worldwide. GDM increases the risks of complications during pregnancy, at delivery and on the longer term, like type 2 diabetes (T2D) and persistent obesity, in mother and child. Moreover, insulin added to diet as the standard care for GDM has disadvantages for mother (maintenance of hyperinsulinaemia, increasing weight and blood pressure) and child (macrosomia, hypoglycaemia) with related adverse pregnancy outcomes. Metformin, as an insulin sensitizer targeting the cause of GDM, may have essential benefits, as suggested by observational studies. However, RCTs with metformin (early positioned in the treatment of GDM) are still lacking. The POEM study is the first Randomized controlled trial (RCT) in GDM to test the hypothesis that metformin, early given from the start of the diagnosis GDM, on top of diet and lifestyle improves clinically relevant pregnancy outcomes in mother and child during pregnancy, at delivery and on the longer term - up to 20 years after birth.


Eligibility

Sex: FEMALEMin Age: 18 YearsMax Age: 45 Years

Inclusion Criteria5

  • Pregnant women with GDM defined as a Fasting Plasma Glucose (FPG) > 5,3 mMol and/or an Oral Glucose Tolerance test (OGTT) with a Plasma glucose (PG) > 7,8 mMol, two hours after the oral intake of 75 gram glucose
  • Written informed consent
  • Age 18-45 years
  • Gestational age at inclusion 16-32 weeks
  • Glycohemoglobin test (HbA1c) at inclusion ≤ 48 mmol/mol (6.5% Hb)

Exclusion Criteria17

  • Diabetes mellitus before pregnancy, except previous GDM
  • Proteinuria: Urine Albumin-to-Creatinine Ratio (UACR) > 35 mg/mmol at screening
  • Malignancy during the last 5 years before inclusion, except non-melanoma skin cancer
  • Psychiatric and/or mood disorder potentially affecting compliance of treatment
  • Chronic liver disease and/or Alanine aminotransferase aspartate transaminase (ASAT) and/or Alanine aminotransferase (ALAT) > 3x Upper Limit of Normal (ULN).
  • Chronic renal failure with a Glomerular filtration rate (GFR) < 45 ml/min/1.73m2
  • Chronic pulmonary failure with hypoxia
  • Significantly uncontrolled hypertension - Systolic blood pressure (SBP) > 160 mm Hg despite medical treatment
  • Chronic treatment with corticosteroids
  • Intolerance for metformin and/or earlier use of metformin in this pregnancy
  • Membership of the POEM study group
  • Severe foetal anomaly at inclusion - like major neural tube and/or cardiac malformation
  • Ruptured membranes
  • Multiple pregnancy
  • Inability to understand or read the Dutch language
  • Bariatric surgery in medical history
  • Hyperemesis gravidarum

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Interventions

DRUGMetformin TEVA 850 mg

At inclusion, patients (N=500) will be randomized 1:1 to metformin vs usual care (850 mg tablets, 3 times daily or, if tolerance is suboptimal, a lower maximally tolerated dose, 1-2 times daily), on top of diet and lifestyle, with an insulin rescue in both arms if needed.


Locations(4)

Martini hospital Groningen

Groningen, Netherlands

University Medical Center Groningen

Groningen, Netherlands

Treant Zorggroep

Hoogenveen, Emmen, Stadskanaal, Netherlands

Medical Center Leeuwarden

Leeuwarden, Netherlands

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NCT02947503


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