Pregnant women with pregestational diabetes taking metformin during the first trimester may be at a higher risk of experiencing pregnancy loss or of their child having major birth defects compared with the general population or women receiving metformin for other indications, according to a study published in the British Journal of Clinical Pharmacology.
Researchers identified individuals from the European Network of Teratology Information Services (ENTIS), as well as from 17 French pharmacovigilance centers, and enrolled them in a multicenter, prospective, observational cohort study to evaluate the risks for birth defects and pregnancy losses in women exposed to metformin (n=471) during the first trimester compared with unexposed women (n=479).
Results demonstrated that women who were exposed to metformin during the first trimester were at a 5.1% (20/392) times higher risk of having a child with a major birth defect compared with a 2.1% higher risk in the reference group (adjusted odds ratio, 1.70; 95% CI, 0.70-4.38). Results were even more severe for those who were taking metformin for pregestational diabetes (7.8%) compared with those without pregestational diabetes (1.7%).
Risk for pregnancy loss for those taking metformin during their first trimester was 20.8%, and it was 10.8% for those in the reference group (adjusted hazard ratio, 1.57; 95% CI, 0.90-2.74). Overall, the risks for women taking metformin with or without pregestational diabetes was 24.0% and 16.8%, respectively. The crude hazard ratio was 2.51 (95% CI, 1.44-4.36) for women with pregestational diabetes and 1.38 (95% CI, 0.74-2.59) for other indications when compared with the reference.
Investigators concluded that “pregnant women with pregestational diabetes on metformin are at an increased risk for multiple adverse pregnancy outcomes.” However, the increased risk for adverse pregnancy outcomes seems to be a result of an underlying diagnosis of diabetes, as women taking metformin for reasons other than diabetes management did not seem to have an increased risk.
Clinicians should use extra caution when prescribing metformin before or during pregnancy for diabetes management because of the increased risk for morbidity and mortality associated with metformin and pregnancy.
Panchaud A, Rousson V, Vial T, et al. Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services [published online January 14, 2018]. Br J Clin Pharmacol. doi: 10.1111/bcp.13481