Evidence from an analysis (2075 offspring, Norway & 15,276 Taiwan of fathers with type 2 diabetes) suggests that paternal use of metformin during period of sperm development is not linked to congenital malformations in offspring (pooled RR 0.89; 95% 0.77 to 1.03), including organ specific malformations (1).
Accompanying editorial editorial notes (2):
- the first major study to examine this association was published in 2022 using population based data from Denmark (n=1,116,779), which found prescription of metformin to fathers during preconception period (for any indication) linked to increased risk of major congenital malformations among offspring, vs insulin
- a subsequent study using same dataset found link between paternal metformin use and increased risk of major congenital malformations persisted when including offspring of mothers with diabetes
- notes that there are now two large population based studies with inconsistent findings
- current findings may not completely lay to rest concerns raised by the Danish analyses, and further confirmatory studies are worthwhile, but at the very least, they provide some reassurance for clinicians, and for fathers-to-be prescribed metformin preconception
Reference:
- Meng L, van Gelder M M H J, Chuang H, Chen L, Hsiao F, Nordeng H M E et al. Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study. BMJ 2024; 387 :e080127
- Gordon H, Hastie R, Lindquist A. Paternal metformin use and congenital malformations in offspring. BMJ 2024; 387 :q1792