Metformin plus insulin for T2D, gestational diabetes does little to improve neonatal outcomes

Treatment with metformin plus insulin early in pregnancy for women with pre-existing type 2 diabetes (T2D) or gestational diabetes falls short of reducing the risk of adverse neonatal outcomes, as shown in the MOMPOD study.

MOMPOD included 831 pregnant adults who had pre-existing T2D or diabetes diagnosed before 23 weeks of gestation. They were randomly assigned to receive insulin with either metformin 1,000 mg or placebo orally twice per day until delivery.

The primary endpoint was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Maternal hypoglycaemia and neonatal fat mass at birth were also evaluated as secondary endpoints.

A total of 794 participants (mean age 32.9 years, 29 percent Black) took at least one dose of the study drug and were included in the primary analysis (397 in the placebo group and 397 in the metformin group).

The incidence of the primary endpoint did not differ between the two groups (71 percent in the metformin group vs 74 percent in the placebo group; adjusted odds ratio, 0.86, 95 percent confidence interval [CI], 0.63–1.19). Preterm birth, neonatal hypoglycaemia, and delivery of a large-for-gestational-age infant were the most frequent events in both groups. The study was terminated at 75 percent accrual for futility in detecting a significant difference in the primary outcome.

Likewise, results for the secondary outcomes and subgroup analyses were similar between the two treatment groups.

Looking at individual components of the composite adverse neonatal outcome, the odds of being large for gestational age were lower in the metformin than in the placebo group (adjusted odds ratio, 0.63, 95 percent CI, 0.46-0.86).