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Volume 6, No. 6, June 2008
Abstract of the Month
Metformin versus insulin for the treatment of gestational diabetes
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.
Rowan JA et al Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15.
http://www.ncbi.nlm.nih.gov/pubmed/18463376
OB/GYN CCC Editorial comment:
We have been waiting a long time for this study
Metformin is a much better physiologic fit for GDM than Glyburide because Metformin essentially sensitizes the muscles to what is an already relatively elevated insulin level. Though metformin is a Pregnancy Class B agent, we had been reluctant to use it widely because it can cross the placenta, and randomized trials to assess the efficacy and safety of its use for this condition were previously lacking till Rowan et al.
Here are few comments from the Ecker and Greene NEJM Editorial:
The Metformin in Gestational Diabetes Trial, which compared Metformin with insulin as initial medical therapy when diet and exercise alone fail to bring blood sugars into an acceptable range for women with gestational diabetes. This noninferiority trial of 751 women showed that infants of mothers in the Metformin group fared no worse than those in the insulin group. Unfortunately, maternal outcomes such as cesarean delivery were not reported, but birth weights were similar in the two groups.
Not surprisingly, patients preferred pills to shots. The main question now is whether Metformin is better or worse than Glyburide, an acceptable alternative pill. On the basis of a previous trial in which 404 women with gestational diabetes achieved equivalent metabolic control using either Glyburide supplemented as necessary with insulin or insulin alone, Glyburide has replaced insulin as the first-line pharmacologic treatment of gestational diabetes in many practices. Although the two oral agents have not been directly compared in trials, it is notable that in the Metformin in Gestational Diabetes Trial, 46% of subjects in the Metformin group required supplemental insulin, whereas in the previous trial, only 4% of women treated with Glyburide needed insulin.
These differences could be the result of varying populations and protocols but deserve further evaluation. Although the Metformin in Gestational Diabetes Trial address adverse outcomes associated with maternal hyperglycemia, gestational diabetes first received attention as a predictor of future diabetes in women. Identifying women at risk for diabetes offers the possibility of intervention to reduce risk, yet frequently these women do not receive recommended follow-up and surveillance. This failure results, perhaps, from a breakdown in communication between obstetricians who diagnose gestational diabetes mellitus and primary care providers who subsequently treat these patients. Recognizing the continuum of risk between hyperglycemia in pregnancy and associated outcomes, we should recommit ourselves to sharing this information so that it can meaningfully affect a woman’s health long after she has completed childbearing.
Ecker JL, Greene MF. Gestational diabetes--setting limits, exploring treatments. N Engl J Med. 2008 May 8;358(19):2061-3.
http://www.ncbi.nlm.nih.gov/pubmed/18463383
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OB/GYN
Dr. Neil Murphy is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Murphy is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to Native or indigenous peoples around the world. Please don't hesitate to contact him by e-mail or phone at 907-729-3154.
