Metformin Tied to Longer Gestation in Women with Preeclampsi
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Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to a study presented at the virtual Society for Maternal–Fetal Medicine (SMFM) 2021 Annual Pregnancy Meeting.

"This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia," researchers at Stellenbosch University in Cape Town, South Africa said.

In the double-blind, randomised placebo-controlled trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks’ gestation. All the women were taking hypertensive drugs. They were randomly assigned to receive 3 g oral metformin XR (extended released) or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.

Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days’ post-randomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance.

But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance.

Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs 7.4 days).

Additionally, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs 4.8 days). In accordance with the safety profile of metformin, women taking the drug experienced more diarrhoea and a trend towards more nausea than those taking the placebo.

There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 grams heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs 34 days for infants in the placebo group.

Based on the findings, the researchers concluded that metformin XR may be a treatment for preterm preeclampsia.

Also, they are now planning to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes.
The findings of prolonged gestation were certainly exciting, but researchers warrant caution before any changes in clinical practice.

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