OB-GYN-L Messages for May, 2008: Metformin versus Insulin for the Treatment of Gestational Diabetes

Metformin versus Insulin for the Treatment of Gestational Diabetes

From: Dean Huffman .

dean@thehuffpeople.net

Sat May 10 17:57:33 2008

ABSTRACT

Background Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking.

Methods We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment.

Results Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 1.00; 95% confidence interval, 0.90 to 1.10). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin.

Conclusions In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment. (Australian New Zealand Clinical Trials Registry number, 12605000311651.)

Gestational diabetes is a complication in about 5% of pregnancies, is increasing in prevalence, and is associated with complications to the pregnancy and a long-term risk of diabetes in both mother and offspring.1,2,3,4,5 Intervention to change lifestyle and, if maternal hyperglycemia persists, treatment with additional insulin have been shown to improve perinatal outcomes.6,7 Women who begin insulin therapy require education to ensure the safe administration of insulin. Use of insulin is also associated with hypoglycemia and weight gain. The use of safe and effective oral agents may offer advantages over insulin.

Oral metformin is a logical option for women with gestational diabetes mellitus. It improves insulin sensitivity, probably by activating AMP kinase, and is not associated with weight gain or hypoglycemia.8,9 Reported outcomes of its use during pregnancy have been favorable10,11,12,13,14,15,16,17,18,19 except for one small, retrospective cohort study20 that showed increased rates of perinatal loss and preeclampsia as compared with insulin treatment. Metformin crosses the placenta and could affect fetal physiology directly.21 Its use in pregnancy remains controversial; to our knowledge, only two small, randomized trials comparing metformin with insulin have been reported to date.22,23

We designed the Metformin in Gestational Diabetes Trial to rule out a 33% increase in a composite of perinatal complications in infants of women treated with metformin as compared with insulin. Our hypotheses were that perinatal outcomes would be similar for both treatments, that women would consider metformin a more acceptable treatment than insulin, and that metformin would improve markers of insulin sensitivity in the mother and baby.

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