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

Gestational Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03651531
• Other study ID #: 1099865-3
• Status: Terminated
• Phase: Phase 3
• Start date: January 3, 2018
• Est. completion date: July 30, 2019

Study information

• Verified date: July 2020
• Source: Women and Infants Hospital of Rhode Island
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: July 30, 2019
• Est. primary completion date: July 30, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes

Intervention

Drug:
• Insulin
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.
• Metformin
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.

Locations

Country	Name	City	State
United States	Women & Infants Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Women and Infants Hospital of Rhode Island

Country where clinical trial is conducted

United States, 

References & Publications (1)

Committee on Obstetric Practice, the American Institute of Ultrasound in Medicine, and the Society for Maternal-Fetal Medicine. Committee Opinion No 700: Methods for Estimating the Due Date. Obstet Gynecol. 2017 May;129(5):e150-e154. doi: 10.1097/AOG.0000000000002046. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hgb A1c	Hgb A1c test	collected at the time of delivery
Secondary	Total daily dose of insulin	Total daily dose of insulin at the end of pregnancy	Will be recorded on hospital admission for delivery
Secondary	Glucose control	Average of fasting and 2 hour postprandial glucose values	patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery.
Secondary	Incidence of maternal hypoglycemia	episodes of maternal hypoglycemia defined as glucose =70 mg/dL	patients will be screened weekly for episodes of hypoglycemia until delivery
Secondary	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	hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection
Secondary	Incidence of maternal side effects	maternal reported medication side effects (i.e. nausea, vomiting, diarrhea)	Will be assessed weekly until delivery
Secondary	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	Will be collected postpartum after delivery
Secondary	Maternal weight gain	weight gain through pregnancy	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
Secondary	Incidence of hypertensive disorder of pregnancy	gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia	from enrollment through study completion (30 days after delivery)
Secondary	Incidence of composite of adverse maternal outcomes	death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis	from enrollment through study completion (30 days after delivery)
Secondary	Breast feeding status	Whether patient is breast feeding or bottle feeding upon discharge from the hospital after delivery	Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery)
Secondary	Mode of delivery	Mode of delivery	recorded at time of delivery
Secondary	Gestational age at delivery	Gestational age at delivery	recorded at time of delivery
Secondary	Infant birthweight (using age/sex matched percentiles)	Infant birthweight (using age/sex matched percentiles)	measured at time of birth
Secondary	Incidence of composite neonatal morbidity	Presence of any of the following: NICU admission, hypoglycemia, hyperbilirubinemia, birth trauma, stillbirth, respiratory distress syndrome, sepsis, neonatal death prior to discharge, 5 minute Apgar score < 7, umbilical artery cord pH <7.10	from delivery through study completion (30 days after delivery)
Secondary	Incidence neonatal hypoglycemia	hypoglycemia requiring intravenous treatment	from delivery through study completion (30 days after delivery)