Paternal metformin use and congenital malformations in offspring

The antidiabetic drug metformin reduces hyperglycaemia by inhibiting hepatic glucose production and increasing insulin sensitivity.1 It is used as initial treatment for type 2 diabetes and off-label to manage a range of other conditions associated with metabolic dysregulation, including obesity and polycystic ovary syndrome.2 More than 24 million prescriptions for metformin were issued in the UK during 2022-23.3

With widespread use comes additional concern for characterising safety at the population level. During pregnancy, metformin crosses the placenta.4 A growing body of literature has consequently focused on characterising any potential effects of maternal metformin use on offspring.5678 Reassuringly, such use has not been convincingly linked with an increased risk of congenital abnormalities.56

By comparison, the potential effect of paternal metformin use on risk of congenital abnormalities among offspring has been understudied. The first major study to examine this association was published in 2022: using population based data from Denmark (n=1 116 779), the authors found that prescription of metformin to fathers …