Back to results

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

Primary Purpose

Gestational Diabetes

Status

Terminated

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Insulin

Metformin

About this trial

This is an interventional treatment trial for Gestational Diabetes focused on measuring metformin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Women & Infants Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

insulin

insulin and metformin

Arm Description

Outcomes

Primary Outcome Measures

Hgb A1c

Hgb A1c test

Secondary Outcome Measures

Total daily dose of insulin

Total daily dose of insulin at the end of pregnancy

Glucose control

Average of fasting and 2 hour postprandial glucose values

Incidence of maternal hypoglycemia

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

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

Incidence of maternal side effects

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

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

Maternal weight gain

weight gain through pregnancy

Incidence of hypertensive disorder of pregnancy

gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia

Incidence of composite of adverse maternal outcomes

death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis

Breast feeding status

Whether patient is breast feeding or bottle feeding upon discharge from the hospital after delivery

Mode of delivery

Gestational age at delivery

Infant birthweight (using age/sex matched percentiles)

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

Incidence neonatal hypoglycemia

hypoglycemia requiring intravenous treatment

Full Information

NCT ID

NCT03651531

First Posted

June 12, 2018

Last Updated

July 22, 2020

Sponsor

Women and Infants Hospital of Rhode Island

1. Study Identification

Unique Protocol Identification Number

NCT03651531

Brief Title

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Terminated

Why Stopped

Trial halted early due to limited ability to recruit participants

Study Start Date

January 3, 2018 (Actual)

Primary Completion Date

July 30, 2019 (Actual)

Study Completion Date

July 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Women and Infants Hospital of Rhode Island

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gestational Diabetes

Keywords

metformin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

insulin

Arm Type

Active Comparator

Arm Title

insulin and metformin

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Hgb A1c

Description

Hgb A1c test

Time Frame

collected at the time of delivery

Secondary Outcome Measure Information:

Title

Total daily dose of insulin

Description

Total daily dose of insulin at the end of pregnancy

Time Frame

Will be recorded on hospital admission for delivery

Title

Glucose control

Description

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.

Title

Incidence of maternal hypoglycemia

Description

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

Time Frame

patients will be screened weekly for episodes of hypoglycemia until delivery

Title

Change in hemoglobin A1c over the course of the pregnancy

Description

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

Title

Incidence of maternal side effects

Description

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

Time Frame

Will be assessed weekly until delivery

Title

Treatment acceptability

Description

Time Frame

Will be collected postpartum after delivery

Title

Maternal weight gain

Description

weight gain through pregnancy

Time Frame

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

Title

Incidence of hypertensive disorder of pregnancy

Description

gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia

Time Frame

from enrollment through study completion (30 days after delivery)

Title

Incidence of composite of adverse maternal outcomes

Description

death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis

Time Frame

from enrollment through study completion (30 days after delivery)

Title

Breast feeding status

Description

Whether patient is breast feeding or bottle feeding upon discharge from the hospital after delivery

Time Frame

Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery)

Title

Mode of delivery

Description

Mode of delivery

Time Frame

recorded at time of delivery

Title

Gestational age at delivery

Description

Gestational age at delivery

Time Frame

recorded at time of delivery

Title

Infant birthweight (using age/sex matched percentiles)

Description

Infant birthweight (using age/sex matched percentiles)

Time Frame

measured at time of birth

Title

Incidence of composite neonatal morbidity

Description

Time Frame

from delivery through study completion (30 days after delivery)

Title

Incidence neonatal hypoglycemia

Description

hypoglycemia requiring intravenous treatment

Time Frame

from delivery through study completion (30 days after delivery)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher Nau, MD

Organizational Affiliation

Women & Infants Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Erika Werner

Organizational Affiliation

Women & Infants Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Women & Infants Hospital

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28426621

Citation

Committee Opinion No 700: Methods for Estimating the Due Date. Obstet Gynecol. 2017 May;129(5):e150-e154. doi: 10.1097/AOG.0000000000002046.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs