Is Paternal Metformin Use Associated with Congenital Malformations?

In a provocative Danish study published 2 years ago, paternal use of metformin just before conception was associated with birth defects among offspring (NEJM JW Gen Med May 15 2022 and Ann Intern Med 2022; 175:665). The theoretical mechanism is an adverse effect on spermatogenesis, which has been noted in some animal studies.

Now, this issue has been examined in another population. Researchers identified 1730 fathers with diabetes in an Israeli health system database who took metformin during the 90 days before conception. In analyses adjusted for potential demographic, cardiometabolic, and maternal confounders, metformin monotherapy was not associated with excess risk for major congenital malformations, compared with no diabetes drug exposu…