Metformin in Women With Type 2 Diabetes in Pregnancy Trial

Mount Sinai Hospital, Canada500 enrolled

Overview

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.

Type 2 diabetes in pregnancy is increasing in prevalence and these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, as an adjunct to insulin, will decrease these adverse outcomes by reducing maternal hyperglycemia, high maternal insulin doses, excessive maternal weight gain and gestational hypertension/pre-eclampsia, all of which should reduce perinatal and neonatal mortality and morbidity. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. This study is an randomized controlled trial (RCT) that adds metformin to insulin, and is a double-blind, placebo-controlled RCT. The investigators believe that neither metformin alone nor insulin alone will effectively treat this population, and therefore our design, which includes the addition of metformin to insulin, will be the most relevant to our patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

500

Conditions

Type 2 Diabetes

Interventions

MetforminDRUG

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

Placebo ComparatorDRUG

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

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Women who are between of 18-45 years of age. 2. (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: * 2 fasting glucose ≥ 7.0 mmol/L, or * 2 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 * 1 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 * 1 fasting glucose ≥ 7.0 mmol/L and 1 two hour (2 hr) ≥ 11.1 on a 75 g Oral Glucose Tolerance Test (OGTT), or * 1 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. 3. Pregnancy gestation between 6+0-22+6 weeks. 4. Live singleton fetus. Exclusion Criteria: 1. 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. 2. Diabetes diagnosed after 20 weeks gestation. 3. Type 1 diabetes. 4. Known intolerance to metformin. 5. 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.

Locations (1)

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

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

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

Time frame: conception to 28 days after birth

Secondary Outcomes

Large for gestational age (LGA) infants

Defined as greater than the 90th percentile for weight, based on the National canadian fetal growth standards for singleton boys and girls.

Time frame: Up to 24 hours after birth

Pregnancy loss

Spontaneous abortion defined as death of a fetus at \<20 weeks gestation; Stillbirth defined as death of a fetus with a birth weight ≥ 500g or at ≥ 20 wks gestational age regardless of birth weight; Neonatal death defined as death of a live born infant within the first 28 days of life or prior to hospital discharge, whichever is later.

Time frame: Up to 40 weeks gestation

Preterm birth

Birth \< 37 weeks gestation

Time frame: Up to 37 weeks gestation

Respiratory distress

Given surfactant via an endotracheal tube and/or requiring assisted positive pressure ventilation within 72 hours after birth.

Time frame: within 72 hours after birth

Neonatal hypoglycemia

A plasma glucose \<2.6 mmol/L on one or more occasions, starting at 30-60 minutes after birth, and necessitating intravenous dextrose within the first 48 hours of life.

Time frame: NICU admission >24 hours

NICU admission >24 hours

Admission to a neonatal intensive or special care unit for \> 24 hours during the initial hospitalization after birth

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.