Metformin does not appear to increase the risk of birth defects when taken by mothers during pregnancy. A large meta-analysis found that women who took metformin actually had a slightly lower rate of congenital malformations compared to those who used insulin, with a 17% relative reduction in risk. However, there is a separate and more surprising concern: when fathers take metformin around the time of conception, their sons may face a higher risk of genital birth defects.
What the Evidence Shows for Mothers
The most comprehensive look at maternal metformin use comes from a meta-analysis that examined birth defects across 11 organ systems. Compared to insulin, metformin was associated with a protective effect on overall congenital malformations. Genetic analysis reinforced this finding, identifying several biological pathways through which metformin may actually reduce the risk of circulatory and musculoskeletal defects. The study’s conclusion: the evidence is consistent with the overall clinical safety of metformin during pregnancy with respect to birth defects.
This is reassuring, but it comes with nuance. Metformin freely crosses the placenta. Fetal blood concentrations range from half to nearly the same level as what’s circulating in the mother. That level of exposure is why researchers continue studying the drug’s effects, even though birth defect rates haven’t raised alarms.
The Paternal Risk That Got Attention
A nationwide Danish cohort study published in the Annals of Internal Medicine found something unexpected. When fathers took metformin during the roughly three-month window when sperm were developing before conception, their male offspring had a 3.4 times higher rate of genital birth defects, primarily a condition called hypospadias (where the opening of the urethra is on the underside of the penis rather than the tip). The study also noted a slight, though not statistically significant, shift toward fewer male offspring among metformin-exposed pregnancies.
This was a single large study, and while the association was strong, it hasn’t yet been confirmed by other research of similar scale. The biological mechanism isn’t fully understood, but metformin may affect how sperm develop or how genes are expressed during that critical formation period. If you or your partner takes metformin and you’re planning a pregnancy, this is worth discussing with a doctor.
How Metformin Affects Folate and B12
One way metformin could theoretically contribute to developmental problems is through its effect on B vitamins. Metformin is associated with lower levels of vitamin B12 and has antifolate-like activity. Both folate and B12 are essential for DNA production and a process called methylation, which controls how genes are turned on and off during fetal development. An imbalance between these two nutrients can lead to genomic instability, meaning cells are more prone to errors when dividing.
This doesn’t mean metformin causes folate deficiency in every person who takes it. But it does mean that women on metformin who become pregnant should pay close attention to their folate and B12 intake. Prenatal vitamins typically contain folic acid, and supplemental B12 may be worth discussing if you’ve been on metformin for a long time.
Metformin and PCOS Pregnancies
Many women searching this topic take metformin for polycystic ovary syndrome rather than diabetes. For this group, a recent systematic review found that continuing metformin through the first trimester was associated with higher pregnancy rates, a possible 36% reduction in miscarriage risk, and a trend toward more live births compared to stopping the drug once pregnant. Women who discontinued metformin after getting a positive pregnancy test actually showed a possible increase in miscarriage risk.
The takeaway from this research is that abruptly stopping metformin at conception may do more harm than continuing it, at least through the first trimester. The benefits of staying on the medication during early pregnancy appear to outweigh the theoretical risks for women with PCOS.
What Medical Guidelines Recommend
The American Diabetes Association’s 2026 Standards of Care state that metformin should not be used as a first-line treatment for diabetes during pregnancy, primarily because it crosses the placenta and may not control blood sugar well enough on its own. Insulin remains the preferred option for managing gestational diabetes and pre-existing diabetes in pregnancy.
For women taking metformin to manage PCOS and induce ovulation, the guidelines recommend discontinuing it by the end of the first trimester. This reflects the current comfort level with early exposure but lingering uncertainty about prolonged use. In practice, many clinicians weigh individual circumstances, including how well blood sugar is controlled, whether the patient can tolerate insulin, and other risk factors.
Long-Term Effects on Children
Beyond birth defects, parents often wonder whether metformin exposure in the womb affects a child’s health later on. A study published in JAMA Pediatrics followed children whose mothers were treated with metformin for gestational diabetes and compared them to children whose mothers used insulin. The two groups were similar in weight, height-for-age, and BMI, with no clinically meaningful differences in growth after adjusting for other factors.
Animal studies have suggested that metformin exposure before birth might offer some metabolic protection, particularly for female offspring, but this hasn’t been consistently observed in humans. Overall, the available evidence does not point to lasting growth or developmental consequences for children exposed to metformin in utero.
Dose and Timing Considerations
One question researchers haven’t been able to answer definitively is whether higher doses of metformin carry more risk than lower ones. Studies have used doses ranging from 1,500 to 3,000 mg per day without finding a clear dose-dependent effect on fetal weight or birth outcomes. However, reliable dose stratification hasn’t been possible in most studies because researchers can’t verify how much of a prescribed medication patients actually took. Until better data exists, the risk profile of metformin in pregnancy doesn’t appear to change meaningfully based on dose within the range typically prescribed.