Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring

BACKGROUND: Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown. OBJECTIVE: To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes. DESIGN: Nationwide prospective registry-based cohort study. SETTING: Denmark from 1997 to 2016. PARTICIPANTS: All liveborn singletons from mothers without histories of diabetes or essential hypertension. MEASUREMENTS: Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings. RESULTS: = 0.073). LIMITATION: Information on underlying disease status was limited. CONCLUSION: Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation. PRIMARY FUNDING SOURCE: National Institutes of Health.