Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus

Phase 3TerminatedNCT03651531

Women and Infants Hospital of Rhode Island1 enrolled

Overview

This study is a prospective, unmasked randomized clinical trial comparing the use of insulin vs combination insulin and metformin for treatment in women diagnosed with gestational diabetes mellitus (GDM). The investigator's hypothesis is that the combination of metformin and insulin will be superior to insulin alone to achieve tight glucose control during pregnancy.

The objective of this study is to compare the effectiveness of insulin alone vs the combination of insulin and metformin in treating patients with gestational diabetes (GDM). Currently, outside of pregnancy, the treatment of type 2 diabetes mellitus (T2DM) with both metformin and insulin is superior to using insulin alone. In pregnancy, insulin alone has traditionally been used, though some advocate the use of metformin alone as primary therapy. There have been no trials published to date specifically comparing combination therapy to insulin alone. Our hypothesis is that the combination of metformin and insulin will improve overall control of blood glucose, the improvement of which has been demonstrated to improve maternal and neonatal outcomes. Control of blood glucose will be determined by hemoglobin A1c at the time of delivery.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gestational Diabetes

Interventions

InsulinDRUG

Weight based insulin will be calculated using 0.7 units/kg/day in the first trimester, 0.8 units/kg/day in the second trimester and 1 units/kg/day in the third trimester. This total insulin will then be divided into short acting insulin and intermediate acting insulin per provider discretion.

MetforminDRUG

Will be initiated at dose of 500 mg twice daily. If glycemic control is suboptimal, the dose of metformin will be increased to 1000 mg twice a day. Metformin will be titrated prior to increases in insulin.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Able to read and write English and/or Spanish and give written consent * Diagnosis of GDM, defined as an abnormal glucose tolerance test performed after 12 weeks gestation using 1 of the 2 criteria below: * 50 gram 1 hour oral diabetes screening testing yielding a result of \> 200 mg/dL * A 100 gram 3 hour oral glucose tolerance testing yielding \>2 abnormal values (normal values defined as fasting blood glucose \< 95, 1 hour \< 180, 2 hour \< 155 and 3 hour \< 140) * Singleton gestation * Gestational age between 12 and 34 weeks and 6 days determined by last menstrual period (LMP) confirmed by ultrasound using criteria set forth by the ACOG (Committee on Obstetric Practice). If LMP is unknown then gestational age must be set by ultrasound prior to 20 weeks gestation. Exclusion Criteria: * Pre-existing DM either by diagnosis preceding pregnancy or hemoglobin A1c \>6.5 collected during the current pregnancy * Uncontrolled chronic hypertension, as this may alter maternal and perinatal outcomes measured. * Multiple gestations * Major fetal anomalies anticipated to require NICU admission * Contraindication to metformin (allergy, history of lactic acidosis, pre-existing renal disease (Cr \>1.5 mg/dL), active liver disease, current alcohol abuse). * Vitamin B12 deficiency, as metformin reduces intestinal absorption of vitamin B12 * Medications known to effect glucose metabolism other than insulin and metformin as this may mask any effect between the two treatments. * Known inability to tolerate metformin.

Locations (1)

Women & Infants Hospital

Providence, Rhode Island, United States

Outcomes

Primary Outcomes

Hgb A1c

Hgb A1c test

Time frame: collected at the time of delivery

Secondary Outcomes

Total daily dose of insulin

Total daily dose of insulin at the end of pregnancy

Time frame: Will be recorded on hospital admission for delivery

Glucose control

Average of fasting and 2 hour postprandial glucose values

Time frame: patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery.

Incidence of maternal hypoglycemia

episodes of maternal hypoglycemia defined as glucose ≤70 mg/dL

Time frame: patients will be screened weekly for episodes of hypoglycemia until delivery

Change in hemoglobin A1c over the course of the pregnancy

If baseline hemoglobin A1c was collected as part of routine care prior to enrollment, this value will be compared to the hemoglobin A1c collected at delivery

Time frame: hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection

Incidence of maternal side effects

maternal reported medication side effects (i.e. nausea, vomiting, diarrhea)

Time frame: Will be assessed weekly until delivery

Treatment acceptability

determined using Diabetes Treatment Satisfaction Questionnaire. Survey includes 8 questions that are answered on a scale of 0-6; 0 indicating the least and 6 the highest level of satisfaction. The individual questions will be compared. Total satisfaction will also be compared by summing the responses to all 8 questions on a composite scale of 0-48

Data from ClinicalTrials.gov

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