Boston—Pregnant women with pregestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes than the general population, but the cause appears to be the disease, not the drug, a new study reports.

The report appears in the British Journal of Clinical Pharmacology. Background information in the study notes that, while metformin is used to treat type 2 diabetes, polycystic-ovary syndrome–associated infertility, and gestational diabetes, human studies evaluating the safety of the common drug in early pregnancy have been scarce.

“Our findings provide the first reassuring evidence that metformin might offer a cheaper and simpler alternative to insulin for the management of pregestational diabetes in pregnancy when effective,” explained lead author Alice Panchaud, PhD, of the Harvard T.H. Chan School of Public Health, Lausanne University Hospital, and Geneva University.

To provide more information, the study team evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester who were matched to an unexposed reference group. The study involved 471 women in the metformin group and 479 in the reference group. 

Results indicate that the risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group, for an adjusted odds ratio (OR) of 1.70; 95%CI 0.70-4.38). Among metformin users, this risk was 7.8% (17/219) in patients with pregestational diabetes and 1.7% (3/173) in those without the diagnosis.

The OR for metformin users with diabetes was 3.95 (95% CI 1.77-9.41), compared to the unexposed group, and for metformin with other indications was 0.83 (95% CI 0.18-2.81). As for the risk of pregnancy losses—spontaneous abortions and stillbirths—it was nearly doubled, 20.8% for women on metformin during the first trimester, compared to 10.8% in the reference group (adjusted hazard ratio [HR] 1.57; 95% CI 0.90-2.74). 

The risks for women on metformin with and without pregestational diabetes were 24.0% and 16.8% respectively, with an adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference.

“Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population,” the researchers conclude. “This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.
« Click here to return to Weekly News Update.