Paternal use of metformin and risk of major congenital malformations: A meta-analysis of 4 studies
Abstract
Metformin is the first-line drug for the treatment of Type 2 diabetes. In 2022, a Danish registry-based study reported a 40% increased risk of major congenital malformations following paternal exposure during spermatogenesis. This raised widespread concern about the use of metformin in males of reproductive age. Three subsequent studies were unable to replicate this finding. We performed a meta-analysis of four observational studies with data from five countries covering more than 11 000 live-born children whose fathers used metformin during spermatogenesis. The pooled risk ratio from an inverse variance-weighted random effects model was 1.03 (95% CI 0.88-1.21). We conclude that paternal exposure to metformin does not confer a meaningfully increased risk of major congenital malformations.
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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