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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. To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes. Nationwide prospective registry-based cohort study. Denmark from 1997 to 2016. All liveborn singletons from mothers without histories of diabetes or essential