Metformin offers no benefit for pre-eclampsia in pregnant women with diabetes

Adding metformin to insulin neither lowers the risk of developing preterm pre-eclampsia nor improves the risk markers of cardiovascular disease (CVD) in pregnant women who have received a diagnosis of diabetes early in pregnancy or have existing type 2 diabetes mellitus (T2DM), according to a study.

Metformin use was not associated with reduced odds of developing pre-eclampsia necessitating delivery before 37 weeks of gestation (adjusted odds ratio [OR], 1.06, 95 percent confidence interval [CI], 0.71–1.57) or before 34 weeks of gestation (adjusted OR, 1.44, 95 percent CI, 0.73–2.28). [SMFM 2024, abstract 27]

Analysis of maternal blood samples collected at 24–30 weeks showed no significant changes in serum concentrations of maternal soluble endoglin (adjusted β, –0.17 ng/mL, 95 percent CI, –2.01 to 1.67), apolipoprotein B (adjusted β, –0.02 mcg/mL, 95 percent CI, –0.12 to 0.07), vascular cell adhesion protein 1 (adjusted β, –90.29 ng/mL, 95 percent CI, –298.0 to 117.5), and high-sensitivity C-reactive protein (adjusted β, –4.03 mcg/mL, 95 percent CI, –11.87 to 3.81).

Pregnant women with diabetes are already at increased risk of pre-eclampsia, and the presence of both conditions raises the risk of CVD, noted one of the study authors Maya Patel of the University of North Carolina at Chapel Hill, North Carolina, US.

Metformin, a common glucose-lowering medication, is used in the treatment of T2DM and to help lower CVD risk outside of pregnancy. However, the findings of the present study indicate that metformin does not offer much for pregnant women with diabetes in terms of reducing the risk of pre-eclampsia and improving markers of CVD risk in the early third trimester, according to Patel.

In a 2021 meta-analysis, metformin use for any indication during pregnancy was associated with lower gestational weight gain and a modest protective effect on the risk of pre-eclampsia but increased gastrointestinal side-effects when compared with other treatments. [Sci Rep 2021;11:9240]

For the present study, Patel and her colleagues performed a secondary analysis of data extracted from a randomized controlled trial wherein metformin was evaluated against placebo in relation to the composite neonatal outcome in participants with singleton pregnancies and insulin-treated early diabetes or T2DM. 

A total of 831 participants had been randomly assigned to receive 1,000-mg metformin twice a day (n=415) or placebo (n=416). Treatment was initiated at 11–23 weeks of gestation and continued until delivery.  

Pre-eclampsia requiring delivery before 37 weeks of gestation occurred in 119 participants (14.3 percent), including 62 (14.9 percent) in the metformin group and 57 (13.7 percent) in the placebo group. Meanwhile, pre-eclampsia requiring delivery before 34 weeks of gestation occurred in 37 participants (4.4 percent), including 22 (5.3 percent) in metformin group and 15 (3.6 percent) in the placebo group.