Trial Outcomes & Findings for Effectiveness of Metformin Compared to Insulin in Pregnant Women With Mild Preexisting or Early Gestational Diabetes (NCT NCT00835861)

NCT ID: NCT00835861

Last Updated: 2017-04-25

Results Overview

Patients self monitored glucose measures throughout pregnancy to aid glycemic control. Fasting morning measures and postprandial measures were taken at 1 hour after breakfast, lunch, and dinner.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery
• Results posted on: 2017-04-25

Participant Flow

Recruitment occurred at two hospitals from July 2008 through March 2010 at one and from January 2009 through December 2009 at the other.

Participant milestones

Measure	Metformin Patients received standard diet and glucose self-monitoring education. Medication naive patients were initiated on Metformin 500 BID or were continued on their current dosage of Metformin if taking prior to pregnancy. Self-reported glucose values were reviewed during each clinic visit and Metformin dosage was titrated up to a maximum of 2250 mg/day as needed for glycemic control. Insulin was added to those not achieving glycemic control with Metformin alone	Insulin Patients received standard diet and glycemic monitoring education. They were started on weight-based Regular and neutral protamine Hagedorn (NPH) insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Self-reported glucose values were reviewed during each clinic visit and insulin dosage was titrated to achieve optimal glycemic control with fasting values \<90 and one hour post prandial values \<130.
Overall Study STARTED	15	16
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effectiveness of Metformin Compared to Insulin in Pregnant Women With Mild Preexisting or Early Gestational Diabetes

Baseline characteristics by cohort

Measure	Metformin n=14 Participants Patients received standard diet and glucose self-monitoring education. Medication naive patients were initiated on Metformin 500 BID or were continued on their current dosage of Metformin if taking prior to pregnancy. Self-reported glucose values were reviewed during each clinic visit and Metformin dosage was titrated up to a maximum of 2250 mg/day as needed for glycemic control. Insulin was added to those not achieving glycemic control with Metformin alone.	Insulin n=14 Participants Patients received standard diet and glycemic monitoring education. They were started on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Self-reported glucose values were reviewed during each clinic visit and insulin dosage was titrated to achieve optimal glycemic control with fasting values \<90 and one hour post prandial values \<130.	Total n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	35.7 years STANDARD_DEVIATION 2.6 • n=5 Participants	29.7 years STANDARD_DEVIATION 4.1 • n=7 Participants	32.7 years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: Daily fasting and 1-hr post prandial measures were taken from time of enrollment until delivery

Population: For 1 infant in each group, the initial neonatal glucose value was missing.

Patients self monitored glucose measures throughout pregnancy to aid glycemic control. Fasting morning measures and postprandial measures were taken at 1 hour after breakfast, lunch, and dinner.

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Blood Glucose Measurements Fasting 18-20 weeks	97.00 mg/dL Interval 93.0 to 100.0	92.38 mg/dL Interval 89.0 to 116.0
Blood Glucose Measurements Fasting 28-30 weeks	92.43 mg/dL Interval 90.0 to 98.0	90.64 mg/dL Interval 84.0 to 106.0
Blood Glucose Measurements Fasting 36-38 weeks	89.49 mg/dL Interval 82.0 to 96.0	85.18 mg/dL Interval 80.0 to 107.0
Blood Glucose Measurements Postprandial throughout enrollment	120.40 mg/dL Interval 115.0 to 129.0	128.62 mg/dL Interval 115.0 to 143.0
Blood Glucose Measurements Postprandial 18-20 weeks	118.40 mg/dL Interval 107.0 to 122.0	120.46 mg/dL Interval 113.0 to 142.0
Blood Glucose Measurements Postprandial 28-30 weeks	119.00 mg/dL Interval 114.0 to 125.0	126.45 mg/dL Interval 115.0 to 137.0
Blood Glucose Measurements Fasting throughout enrollment	97.38 mg/dL Interval 92.0 to 101.0	95.04 mg/dL Interval 86.0 to 115.0
Blood Glucose Measurements Postprandial 36-38 weeks	122.59 mg/dL Interval 118.0 to 130.0	125.25 mg/dL Interval 112.0 to 138.0

SECONDARY outcome

Timeframe: Throughout pregnancy until hospital discharge following delivery.

Maternal complications were stillbirths, major malformations, shoulder dystocia, or postpartum hemorrhage requiring transfusion.

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Number of Patients With Obstetric Complications	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline throughout pregnancy until last prenatal visit.

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Maternal Weight Gain	0.28 kg/week Interval 0.11 to 0.38	0.30 kg/week Interval 0.18 to 0.47

SECONDARY outcome

Timeframe: Time of delivery through hospital discharge

Population: For 1 infant in each group, the initial neonatal glucose value was missing.

Initial neonatal glucose < 40 mg/dL

Outcome measures

Measure	Metformin n=13 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=13 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Number of Babies With Neonatal Hypoglycemia	2 Number of babies	0 Number of babies

SECONDARY outcome

Timeframe: 1st, 2nd, and 3rd trimester

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester 2nd trimester	5.6 percentage of glycosolated hemoglobin Interval 5.4 to 5.8	5.5 percentage of glycosolated hemoglobin Interval 5.2 to 6.1
Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester 3rd trimester	5.9 percentage of glycosolated hemoglobin Interval 5.5 to 6.0	5.6 percentage of glycosolated hemoglobin Interval 5.3 to 6.4
Glycosylated Hemoglobin (HbA1c) by Pregnancy Trimester 1st trimester	5.8 percentage of glycosolated hemoglobin Interval 5.4 to 6.5	6.2 percentage of glycosolated hemoglobin Interval 5.7 to 7.5

SECONDARY outcome

Timeframe: Baseline throughout pregnancy until time of delivery

NUMBER OF ASSESSMENTS OF FASTING GLUCOSE VALUES <95

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) Throughout enrollment; n=1634, 1432	48 percent of glucose values Interval 0.38 to 0.67	58 percent of glucose values Interval 0.17 to 0.81
Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) 18-20 weeks; n=148, 259	42 percent of glucose values Interval 0.31 to 0.57	64 percent of glucose values Interval 0.0 to 0.83
Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) 28-30 weeks; n=253, 201	64 percent of glucose values Interval 0.29 to 0.85	62 percent of glucose values Interval 0.23 to 1.0
Percent of Glucose Values at or Below Fasting Goal (<95 mg/dL) 36-38 weeks; n=115, 83	76 percent of glucose values Interval 0.54 to 0.93	96 percent of glucose values Interval 0.2 to 1.0

SECONDARY outcome

Timeframe: Baseline throughout pregnancy until time of delivery

NUMBER OF ASSESSMENTS OF POSTPRANDIAL GLUCOSE VALUES <130

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) Throughout enrollment; n=4195, 3796	69 percent of glucose values	61 percent of glucose values
Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) 18-20 weeks; n=368, 428	72 percent of glucose values	67 percent of glucose values
Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) 28-30 weeks; n=652, 559	71 percent of glucose values	58 percent of glucose values
Percent of Glucose Values at or Below Postprandial Goal (<130 mg/dL) 36-38 weeks; n=272,228	66 percent of glucose values	65 percent of glucose values

SECONDARY outcome

Timeframe: Baseline throughout pregnancy until time of delivery

Maternal glucose < 60 mg/dL

Outcome measures

Measure	Metformin n=14 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Number of Episodes Maternal Hypoglycemia	1 Number of episodes	7 Number of episodes

SECONDARY outcome

Timeframe: Delivery until hospital discharge

Population: For 1 infant in the metformin group, the "adverse neonatal outcome" data was missing.

Resuscitation in the delivery room, preterm birth < 37 weeks, neonatal intensive care unit care, birth injury or diagnosis of neonatal complication, glucose infusion, antibiotics, or phototherapy.

Outcome measures

Measure	Metformin n=13 Participants Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 Participants Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Number of Babies With Adverse Neonatal Outcomes	4 number of babies	7 number of babies

Adverse Events

Metformin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Insulin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metformin n=14 participants at risk Standard diet and glucose self-monitoring education. Initiated on Metformin 500 BID if medication naïve, or continued on their current dosage of Metformin if taking it prior to pregnancy. Dosage titrated to a maximum of 2250 mg/day based on review of self-reported fasting and post prandial glucose values during visits. .NPH Insulin treatment added for those unable to achieve glycemic control with Metformin alone.	Insulin n=14 participants at risk Standard diet and glycemic monitoring education. Initiated on weight-based Regular and NPH insulin at a total dosage of 0.7units/kg in the first trimester or 0.8units/kg in the second trimester divided as 2/3 of the total dosage (with 2/3 given as NPH and 1/3 given as Regular) administered before breakfast and 1/3 of the total dosage (with 1/2 given as NPH and 1/2 given as Regular) administered with dinner. Dosage titrated during visits to achieve optimal glycemic control with fasting values \<90 mg/dL and 1-hr post prandial values \< 130 mg/dL.
Pregnancy, puerperium and perinatal conditions Intrauterine fetal demise	7.1% 1/14 • Number of events 1 • From July 2008 through March 2010	0.00% 0/14 • From July 2008 through March 2010

Other adverse events

Adverse event data not reported

Additional Information

M. Ashley Hickman Zink

Maternal-Fetal Medicine and Obstetrics at UT Southwestern

Phone: 469-303-3591

Email: m.ashley.hickman@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place