Sunday , October 22 2017
Home / Resources / Articles / Metformin Alone or With Insulin Safe in Gestational Diabetes 

Metformin Alone or With Insulin Safe in Gestational Diabetes 

In pregnant women with gestational diabetes, metformin alone or metformin supplemented with insulin did not increase perinatal complications vs insulin alone, according to the results of a new study. "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," write Janet A. Rowan, MB, ChB, from Auckland City Hospital in Auckland, New Zealand, and colleagues from the Metformin in Gestational Diabetes Trial Investigators.

In this trial, 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation were randomized to receive open treatment with metformin plus supplemental insulin if needed or insulin alone. The main endpoints were a composite outcome of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score of less than 7, or prematurity.

The trial was designed to rule out a 33% increase (from 30% – 40%) in this composite endpoint in infants of women treated with metformin vs those treated with insulin. Secondary endpoints were neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and tolerability and acceptability of treatment.

Of 363 women randomized to receive metformin, 92.6% continued to receive metformin until delivery, and 46.3% received supplemental insulin. The primary composite endpoint occurred in 32.0% of the group randomized to receive metformin and 32.2% of those randomized to receive insulin (relative risk [RR], 1.00; 95% confidence interval [CI], 0.90 – 1.10).

Compared with women in the insulin group, more women in the metformin group stated that they would choose to receive their assigned treatment again (76.6% vs 27.2%; P < .001). Other secondary endpoints were similar in both groups, and there were no serious adverse events associated with metformin use.

"In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin," the study authors write. "The women preferred metformin to insulin treatment."

Limitations of this study include open-label design; lack of blinding; use of a superiority design to determine whether insulin was superior to metformin, with acceptance rather than proof of the null hypothesis (that there is no difference between treatments); use of a composite outcome that included outcomes of differing clinical significance; and lack of follow-up data for offspring.

"Further follow-up data are needed to establish long-term safety," the study authors conclude.

In Conclusion,  women with gestational diabetes, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment.

"The main question now is whether metformin is better or worse than glyburide, an acceptable alternative pill," Drs. Ecker and Greene write. "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. . . . 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."

Practice Pearls:

  • In the Metformin in Gestational Diabetes Trial, metformin (alone or with supplemental insulin) was not associated with increased perinatal complications vs insulin. The primary composite endpoints occurred in 32.0% of the group randomized to receive metformin and 32.2% of those randomized to receive insulin.
  • In this trial, the women preferred metformin to insulin treatment. Compared with women in the insulin group, more women in the metformin group stated that they would choose to receive their assigned treatment again. There were no serious adverse events associated with metformin use.

N Engl J Med. May 8, 2008;358:2003-2015, 2061-2063.