乌鸦传媒

Adding metformin to insulin treatment for pregnant women with preexisting type 2 or gestational diabetes did not reduce composite neonatal adverse outcomes, according to the randomized MOMPOD trial.

The composite outcome -- encompassing perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy -- occurred at similar rates in the metformin and placebo groups (71% vs 74%, adjusted OR 0.86, 95% CI 0.63-1.19).

However, metformin was associated with fewer large-for-gestational-age infants (26% vs 36%, OR 0.63, 95% CI 0.46-0.86), reported Kim Boggess, MD, of the University of North Carolina at Chapel Hill, and co-authors in .

The difference in birthweight was around 180 g, but this reduction did not translate into fewer operative deliveries in the metformin group, Boggess noted in an interview with 乌鸦传媒.

"In the case of patients with type 2 diabetes, we knew that based on established evidence that glycemic control is critical to improving ... both maternal and infant outcomes," Boggess said. "But we didn't really know the best way to achieve maternal glycemic control."

Guidelines recommend insulin as first-line pharmacotherapy for preexisting type 2 diabetes, and metformin for patients who cannot use insulin or decline to do so.

MOMPOD's findings counter those of the prior , conducted in Canada and Australia, that found metformin improved maternal glycemic control and resulted in less maternal weight gain, less neonatal adiposity, fewer cesarean deliveries, and more small-for-gestational-age neonates.

In an accompanying , MiTy investigator Denice Feig, MD, of the University of Toronto, put the findings together: "The results of MOMPOD suggest that although still useful in reducing births of large-for-gestational-age infants and improving glycemic control, other benefits of metformin use in those with type 2 diabetes during pregnancy may be diminished in some populations."

Third-trimester hemoglobin A1c was 5.97% with metformin versus 6.22% with placebo, but the difference was of borderline significance (geometric mean ratio 0.96, 95% CI 0.93-1.00) and it was measured in only 39% of trial participants.

Feig and Boggess both noted that the differences between trial findings should be further investigated. Boggess said her team is working on combining the data from MiTy and MOMPOD trials for an individual patient meta-analysis. They're also hoping to see whether there are positive or negative infant effects into childhood.

was a 17-site, double-blinded randomized clinical trial. From June 2017 to November 2021, participants were enrolled in the study, with a pause April-September 2020 because of the pandemic. All final visits were complete by May 2022.

The cohort included adults ages 18 to 45 who had a singleton pregnancy of 10 to 22 weeks, 6 days gestation at baseline; all had preexisting type 2 diabetes requiring insulin or had diabetes diagnosed by 23 weeks gestation. The 794 participants were randomized 1:1 to receive insulin plus 1,000 mg metformin or insulin plus placebo.

Participants identified their heritage as 52% Hispanic, 29% Black, 14% white, and 3% Asian. The mean age was 32.9 years. Most had preexisting type 2 diabetes (78%), and the rest were diagnosed early in pregnancy (21%).

Preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant were the most common primary outcome in both groups. Among adverse events, both groups experienced nausea and vomiting at similar rates, but the metformin group reported higher instances of diarrhea (28 vs 12%, P<0.01).

The study was stopped at 75% of planned enrollment because of futility, which in combination with the pandemic-related pause, limited the measurability of metformin's impact on less common outcomes. Authors also noted that results were similar across BMI subgroup analyses, but those with obese BMIs were overrepresented in the metformin group. Poor adherence might have been underreported, since it was measured by self-report.

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