Metformin: One pill takes care of pre-eclampsia risk, glucose control in pregnancy

In pregnant women with prediabetes or pregestational type 2 diabetes (T2D), metformin also yields protective effects on the risk of pre-eclampsia, as shown in two studies presented at the Society for Maternal-Fetal Medicine (SMFM) 40th Annual Pregnancy Meeting.

“[The glucose-lowering drug] has been found to have a role in promoting vascular remodelling and angiogenesis, which may reduce the risk of developing pre-eclampsia,” according to a team of researchers who conducted both studies. “These data suggest there may be benefit to metformin administration beyond glycaemic control in [the population of pregnant women with elevated blood sugar levels].”

The analysis involved a retrospective cohort of women with singleton pregnancies complicated by prediabetes (prepregnancy or first trimester haemoglobin A1c between 5.7 percent and 6.4 percent; n=248) or T2D (n=254) with or without exposure to metformin (prediabetes: n=95 and n=163, respectively; T2D: n=132 and n=122, respectively). The primary outcome was a hypertension composite defined as gestational hypertension, pre-eclampsia with or without severe features, or HELLP syndrome.

In the prediabetes cohort, the primary outcome was similar between women exposed and not exposed to metformin. However, the drug was associated with a significantly lower risk of pre-eclampsia with severe features (adjusted odds ratio [aOR], 0.32, 95 percent confidence interval [CI], 0.11–0.95). This benefit was more pronounced in women who initiated treatment early in pregnancy (vs nonexposure: aOR, 0.17, 95 percent CI, 0.04–0.87). [SMFM 2020, abstract 499]

In the T2D cohort, the likelihood of developing the hypertension composite was markedly lower among metformin users vs nonusers (22.7 percent vs 33.1 percent; aOR, 0.53, 95 percent CI, 0.29–0.96). Exposure to the glucose-lowering drug likewise cut the incidence of pre-eclampsia with severe features (12.1 percent vs 20.7 percent; aOR, 0.38, 95 percent CI, 0.18–0.81). There were no significant between-group differences observed in preterm birth prior to 34 or 37 weeks, foetal growth restriction, or birth weight. [SMFM 2020, abstract 994]

Metformin was being taken at conception or introduced in the first trimester in 52 percent and 91 percent of users in the prediabetes and T2D cohorts, respectively. Moreover, in the latter cohort, users had a higher prepregnancy body mass index and were more likely to have chronic hypertension and prior hypertensive disorder of pregnancy compared with nonusers.

Current evidence suggests that the glucose-lowering drug exerts wide-ranging beneficial effects through the following mechanisms of action: suppression of intracellular metabolic activity of mitochondria and the cellular nutrient-sensing system mediated by mTOR (mammalian target of rapamycin). [Am J Obstet Gynecol 2017;217:282-302]

Taken together, the findings confirm that the beneficial effects of metformin extend to reducing the risk of pre-eclampsia with severe features, the researchers said.

 “Th[e] study also points to the importance of recognizing glucose intolerance early in pregnancy, as patients with prediabetes have additional risk factors for obstetric complications,” they added.