Clinical trial NCT03651531: Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus
Official title: Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gestational Diabetes
Keywords: metformin
Lead sponsor: Women and Infants Hospital of Rhode Island
Sponsor class: OTHER
First posted: 2018-08-29
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hgb A1c
timeFrame: collected at the time of delivery
Secondary outcomes:
measure: Total daily dose of insulin
timeFrame: Will be recorded on hospital admission for delivery
measure: Glucose control
timeFrame: patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery.
measure: Incidence of maternal hypoglycemia
timeFrame: patients will be screened weekly for episodes of hypoglycemia until delivery
measure: Change in hemoglobin A1c over the course of the pregnancy
timeFrame: hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection
measure: Incidence of maternal side effects
timeFrame: Will be assessed weekly until delivery
measure: Treatment acceptability
timeFrame: Will be collected postpartum after delivery
measure: Maternal weight gain
timeFrame: This will be calculated as the difference from the weight measured at the inital prenatal visit (the specific timing of which is patient dependant) and at the time of admission for delivery
measure: Incidence of hypertensive disorder of pregnancy
timeFrame: from enrollment through study completion (30 days after delivery)
measure: Incidence of composite of adverse maternal outcomes
timeFrame: from enrollment through study completion (30 days after delivery)
measure: Breast feeding status
timeFrame: Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery)
measure: Mode of delivery
timeFrame: recorded at time of delivery
measure: Gestational age at delivery
timeFrame: recorded at time of delivery
measure: Infant birthweight (using age/sex matched percentiles)
timeFrame: measured at time of birth
measure: Incidence of composite neonatal morbidity
timeFrame: from delivery through study completion (30 days after delivery)
measure: Incidence neonatal hypoglycemia
timeFrame: from delivery through study completion (30 days after delivery)
Other outcomes:
Locations:
city: Providence
country: United States
facility: Women & Infants Hospital
state: Rhode Island
Study officials:
affiliation: Women & Infants Hospital
name: Christopher Nau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women & Infants Hospital
name: Erika Werner
role: PRINCIPAL_INVESTIGATOR
References:
citation: Committee Opinion No 700: Methods for Estimating the Due Date. Obstet Gynecol. 2017 May;129(5):e150-e154. doi: 10.1097/AOG.0000000000002046.