A large study, which tracked 3m pregnancies in Norway and Taiwan, found that men can take the commonly prescribed diabetes drug metformin without worrying about causing birth defects in their children, according to the researchers.
They said they found no association between birth defects and metformin taken by the fathers during the three months before conception, which is the period of sperm development, reports Reuters.
The relatively inexpensive generic metformin is typically the first drug prescribed for Type 2 diabetes, the most prevalent form of the disease.
An earlier, 2022 study from Denmark had suggested metformin was associated with a 1.4 times greater risk of birth defects in boys whose fathers were taking the drug. Studies conducted since have not confirmed that association.
In June, a pair of studies published in Annals of Internal Medicine suggested that neither maternal nor paternal metformin use increases the risk of congenital malformations
The use of data from two different populations in Norway and Taiwan strengthens the latest study’s results, said Dr Allan Pacey, an expert in male reproductive health issues at the University of Manchester in Britain.
The new finding – published in The BMJ – that no link exists between a father’s metformin use and birth defects “makes sense because there was never any plausible biological mechanism which might have led us to this conclusion”, he added.
Study details
Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study
Lin-Chieh Meng, Marleen van Gelder, Hedvig Nordeng et al.
Published in The BMJ on 16 October 2024
Abstract
Objective
To evaluate the association between paternal metformin use and risk of congenital malformations in offspring.
Design
Population based, cross national cohort study.
Setting
Norway and Taiwan.
Participants
A total of 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18.
Main outcome measures
The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach.
Results
Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses.
Conclusions
The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children.
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