Metformin in Women With Type 2 Diabetes in Pregnancy Trial

NCT01353391 | Completed Phase 3 DMC

• 1 other identifier: MOP-106678
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, in addition to treatment with insulin, will help with blood sugar control, lower the dose of insulin needed, lower weight gain, and improve baby outcomes.

Conditions

Type 2 Diabetes

Keywords

Diabetes; MiTy; Metformin in Women; Type 2 Diabetes Pregnancy

Outcome Measures

Primary Outcomes (1)

• A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.

  conception to 28 days after birth

Secondary Outcomes (21)

• Large for gestational age (LGA) infants

  Up to 24 hours after birth

• Pregnancy loss

  Up to 40 weeks gestation

• Preterm birth

  Up to 37 weeks gestation

• Respiratory distress

  within 72 hours after birth

• Neonatal hypoglycemia

  NICU admission >24 hours

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Drug: Placebo Comparator

Interventions

Metformin DRUG

500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy

Metformin

Placebo Comparator DRUG

500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy

Placebo

Eligibility Criteria

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

You may qualify if:

• Women who are between of 18-45 years of age.
• (i). Women diagnosed with type 2 diabetes prior to pregnancy, OR (ii). Women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation, defined as women presenting with gestational diabetes before 20 weeks gestation with various combinations, as per Canadian Diabetes Association, including:
• fasting glucose ≥ 7.0 mmol/L, or
• HbA1c of ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the Diabetes Control and Complications Trial (DCCT) assay, or
• fasting glucose ≥7.0 mmol/L and 1 HbA1c ≥ 0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay, or
• fasting glucose ≥ 7.0 mmol/L and 1 two hour (2 hr) ≥ 11.1 on a 75 g Oral Glucose Tolerance Test (OGTT), or
• HbA1C ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay and 1 two hour (2 hr) ≥ 11.1 on a 75 g OGTT.
• Pregnancy gestation between 6+0-22+6 weeks.
• Live singleton fetus.

You may not qualify if:

• Women who are not on insulin. Women who are on oral hypoglycemic agents will be taken off at the start of the trial and started on insulin prior to randomization.
• Diabetes diagnosed after 20 weeks gestation.
• Type 1 diabetes.
• Known intolerance to metformin.
• Contraindications to metformin use which include:
• (i). Renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance \<60 ml/min) , (ii). Moderate to severe liver dysfunction (defined as liver enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) greater than 3 times the upper limit of normal), (iii). Shock or sepsis, and (iv.) Previous hypersensitivity to metformin.
• f. Women with significant gastrointestinal problems such as severe vomiting requiring IV fluids or hospitalization, or active Crohn's or colitis.
• g. Previous participation in the trial. h. Women who have a fetus with a known potentially lethal anomaly will be excluded. Information regarding congenital anomalies diagnosed after randomization will be recorded.
• i. Known higher order pregnancies (twins, triplets, etc). These women will be excluded as they have a higher rate of adverse outcomes and we want to avoid any inequalities if they are unequally distributed between the groups.
• j. Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis.
• k. History of diabetic ketoacidosis or history of lactic acidosis. l. Presence of excessive alcohol intake, acute or chronic. m. Presence of congestive heart failure or history of congestive heart failure.

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• University Health Network, Toronto: collaborator
• Sunnybrook Research Institute: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

The Centre for Mother, Infant, and Child Research, Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (2)

• Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, Fantus IG, Hutton E, Armson AB, Lipscombe LL, Simmons D, Barrett JFR, Karanicolas PJ, Tobin S, McIntyre HD, Tian SY, Tomlinson G, Murphy KE; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Oct;8(10):834-844. doi: 10.1016/S2213-8587(20)30310-7.

  PMID: 32946820 DERIVED

• Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, Ohlsson A, Ryan EA, Fantus IG, Armson AB, Lipscombe LL, Barrett JF; MiTy Collaborative Group. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial. BMC Pregnancy Childbirth. 2016 Jul 19;16(1):173. doi: 10.1186/s12884-016-0954-4.

  PMID: 27435163 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Denice Feig, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 13, 2011
• Study Start: May 25, 2011
• Primary Completion: June 5, 2019
• Study Completion: June 5, 2019
• Last Updated: March 3, 2020

Record last verified: 2020-03

Locations

CA (1)