On this week’s episode of Lifespan News, Ryan O’Shea discusses some alarming research suggesting that metformin is linked to birth defects.
The common diabetes drug metformin is also used within the life extension community, where some people choose to take it for its perceived longevity benefits. However, it may be worth reconsidering that. A large-cohort population study from Denmark has linked metformin to a 40% increase in the risk of birth defects when taken by fathers within three months of conception. We’ll get into the study in this episode of Lifespan News!
Metformin is an anti-diabetes drug that drew geroscientists’ attention after studies had shown that it reduces all-cause mortality and alleviates diseases of aging. One crucial study even found that diabetic patients who took metformin had a lower risk of all-cause mortality than healthy people who were not on metformin.
Another study showed that metformin extends life in mice, but then metformin didn’t do so well in the ITP, or Intervention Testing Program trials, although it was shown to enhance the life-prolonging effect of rapamycin.
Many geroscientists still think there is a chance that metformin can extend lifespan in humans, and the drug is currently the subject of TAME, Targeting Aging with Metformin, the first large-scale human trial of a potentially life-extending drug.
But the results of this new study may make some people think twice about taking it. By analyzing a large cohort in Denmark, the scientists detected an increased prevalence of birth defects in children whose fathers were on metformin prior to conception.
Drawing from a giant health database, the researchers identified fathers with diabetes who had a history of taking one or more of the anti-diabetes medications insulin, metformin, and sulfonylurea. Of more than one million offspring, 3.3% had major birth defects, but metformin-exposed children – those of fathers who took metformin three months prior to conception – were 40% more likely to have birth defects. However, if the father stopped taking metformin one year or more prior to conception, the drug had no effect on the prevalence of birth defects.
The researchers did attempt to account for confounding variables in the study. Diabetic mothers and mothers with diagnosed hypertension were excluded. The analysis was also restricted to maternal age at birth of 35 and paternal age at birth of 40. Parental education and income levels and maternal smoking status during pregnancy were also accounted for.
On the other hand, the researchers had no access to other potentially relevant parameters such as diet or obesity status. Additionally, the researchers only knew whether the father redeemed a prescription for metformin but not whether the drug was taken as prescribed.
Despite this, the evidence is hard to ignore. Genital defects that appeared solely in boys constituted a disproportionate amount of birth defects in metformin-exposed children. However, unexposed siblings of exposed offspring did not have an increased risk of birth defects. Insulin showed no correlation with birth defects, and while sulfonylurea did show some correlation, the results were not statistically significant.
It is worth noting that, overall, metformin has a great safety record and has been included in the World Health Organization’s list of essential medicines. However, metformin was also recently categorized as a “known or suspected endocrine disrupting contaminant of emerging concern” in another study that was focused on chemical contamination of the surface and groundwater – quite different from what we’re focusing on here, but something to be aware of.
How serious is this? Well, we’re not sure yet. This study does not establish a causal relationship, and it will be interesting to see if another study corroborates these findings. Also, since birth defects are fairly rare, the risk is still low even after a 40% increase.
In the context of metformin and life extension, Dr. Nir Barzilai, the lead scientist of the TAME trial, pointed out during an interview with Lifespan.io that it would make most sense to consider starting metformin around age 50, an age at which many people have stopped considering birth defects in potential children.
This study appears valuable, but it raises more questions than it answers. The researchers took reasonable steps to get quality data, but there were limitations that could not be overcome. Ultimately, more studies are needed – and we’ll be watching closely for those results. Make sure to subscribe to stay up to date, and we’ll see you next time on Lifespan News!