Cohort Studies: Metformin During Early Pregnancy or Spermatogenesis is Safe Regarding Congenital Malformation Risks – Ann Intern Med

Study Design and Population: Two observational cohort studies assessed the safety of metformin, focusing on early pregnancy and paternal use during spermatogenesis. The first study involved 12,489 pregnant women with pregestational type 2 diabetes, comparing those on insulin monotherapy to those on insulin plus metformin. The second study analyzed 383,851 live births in Israel, examining the impact of paternal metformin use during spermatogenesis on congenital malformations in newborns.

Main Findings: The first study found no significant increase in the risk of nonlive births when continuing metformin in early pregnancy compared to switching to insulin monotherapy. The risk of congenital malformations was also comparable between the two groups. The second study showed that paternal metformin use in monotherapy did not raise the risk of major congenital malformations, though a slight risk increase was observed with metformin in polytherapy, potentially due to underlying cardiometabolic conditions.

Implications for Practice: These findings suggest that metformin use, either during early pregnancy or spermatogenesis, poses minimal risk for congenital malformations. However, clinicians should consider the overall cardiometabolic profile and diabetes management when prescribing metformin, especially in combination with other antidiabetic medications.

References:

Chiu YH et al. (2023). Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations: Emulating a Target Trial Using Real-World Data. Annals of Internal Medicine, 177(7). DOI: 10.7326/M23-2038.

Rotem RS et al. (2023). Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns. Annals of Internal Medicine, 177(7). DOI: 10.7326/M23-1405.