Metformin Versus Insulin for the Treatment of Gestational Diabetes

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, 0.99; 95% confidence interval, 0.80 to 1.23). 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.

Metformin Compared with Insulin in the Treatment of Pregnant Women with Overt Diabetes: A Randomized Controlled Trial

“…12,13,17,18 More recently, a large randomized controlled trial has compared metformin to insulin in the treatment of gestational diabetes. 4 Although, metformin use resulted in a higher rate of failure to adequately control blood glucose, it was well tolerated and not associated with increased complications. Our results are consistent with prior studies that have shown a metformin failure rate of 46% 4 and 35% 19 in gestational diabetes without a consistent increase in adverse outcome.…”

The Effect of Maternal Obesity on Pregnancy Outcomes of Women with Gestational Diabetes Controlled with Diet Only, Glyburide, or Insulin

“…Because of convenience and ease of administration, oral hypoglycemic agents (OHA) are often preferred by patients over insulin injections. 7 The safety of OHA has been presumed based on in vitro and in vivo studies. 8 The OHA glyburide has become increasingly popular for blood glucose management in women diagnosed with GDM.…”

Managing gestational diabetes: timing, selection and use of pharmacotherapy

“…Recently, short-and some long-term outcomes concerning metformin exposure for GDM have become available, which is important information as metformin is known to cross the placenta to the fetal compartment in significant concentrations [43]. Rowan et al demonstrated equivalence in a randomized trial between metformin and insulin for GDM; however, over 40% of women randomized to metformin required some insulin supplementation [44]. Glycemic control was similar, as were maternal and neonatal outcomes, but there was a high rate of metformin failure (46%) requiring supplemental insulin to achieve euglycemia.…”

“…Advantages to metformin were noted, including decreased maternal weight gain as well as increased patient satisfaction. The former is particularly important for future health given the propensity for women with GDM to have weight concerns prior to pregnancy [44]. Unlike the experience with glyburide, the offspring of the original randomized controlled trial are being followed-up after 2 and 5 years, with high-quality neonatal data to assure no unexpected long-term consequences to the offspring.…”