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November 09, 2021
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Extended-release metformin prolongs pregnancy in women with preterm preeclampsia

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Extended-release metformin prolonged gestation compared with placebo in women who had preterm preeclampsia, according to results of a randomized controlled trial.

“This is the first study” to yield such a finding, Catherine Cluver, MBChB, FCOG, PhD, an associate professor and maternal fetal medicine subspecialist in the department of obstetrics and gynecology at Stellenbosch University in Cape Town, South Africa, told Healio Primary Care.

The researchrers found that the median prolongation of gestation was 17.5 days in the metformin cohort compared with 7.9 days in the placebo cohort.
Reference: Culver CA, et al. BMJ. 2021;doi: 10.1136/bmj.n2103.

The American College of Obstetricians and Gynecologists has previously estimated that preeclampsia “complicates” between 2% and 8% of pregnancies worldwide. In the United States, a woman’s risk for preeclampsia increased nearly sevenfold from 1980 to 2003.

In the new study, Cluver and colleagues randomly assigned 180 South African women undergoing preeclampsia management in a 1:1 ratio to receive 3 g of oral extended-release metformin or placebo in divided doses daily until they gave birth.

The median gestation age was 29 weeks and 3 days in the metformin cohort and 29 weeks and 5 days in the placebo cohort, while the median age was 29 years in the metformin cohort and 27 years in the placebo cohort. Black women accounted for 66% of the metformin recipients and 61% of placebo recipients.

The median time from randomization to delivery was 17.7 days in the metformin cohort vs. 10.1 days in the placebo cohort. Two women — one from each cohort — withdrew from the study. Of the women who remained, 48 in the metformin cohort and 27 in the placebo cohort either lowered their dosage or stopped taking it entirely.

The findings, published in The BMJ, showed that median prolongation of gestation was 17.5 days (interquartile range [IQR] = 5.4-28.7) in the metformin cohort compared with 7.9 days (IQR = 3-22.2) in the placebo cohort for a median difference of 9.6 days (geometric mean ratio = 1.67; 95% CI, 1.16-2.42).

Among the women who received the full dosage from randomization to delivery, the median prolongation of gestation was 16.3 days (IQR = 4.8-28.8) in the metformin cohort compared with 4.8 days (IQR = 2.5-15.4) in the placebo cohort, yielding a median difference of 11.5 days (geometric mean ratio = 1.8; 95% CI, 1.14-2.88). There was a nonsignificant increase in birth weight and decrease in time spent in the neonatal nursery among infants born to women in the metformin cohort, according to Cluver and colleagues.

The researchers also reported that although no serious adverse events were observed in either group, women in the metformin cohort experienced diarrhea more frequently. There were no significant differences between the cohorts regarding composite maternal, fetal and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor and soluble endoglin.

Cathy Cluver

“We were hoping that metformin could prolong gestation for preterm preeclampsia,” Cluver told Healio Primary Care. “To find that women who took metformin gained a further weeklong prolongation of pregnancy was more than we had hoped for.”

References

ACOG. Practice bulletin on gestational hypertension and preeclampsia. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/06/gestational-hypertension-and-preeclampsia. Accessed Nov. 4, 2021.

Culver CA, et al. BMJ. 2021;doi: 10.1136/bmj.n2103.