 The common diabetes drug Metformin is also used within the life extension community for its perceived longevity benefits. However, some may want to reconsider using it. A large cohort population study from Denmark has linked Metformin to a 40% increase in 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 first drew geroscientist 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, although it was shown to enhance the life-prolonging effect of rapamycin. Many geroscientists still think that there's a chance that Metformin can extend lifespan in humans, and the drug is currently the subject of TAIM, 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 before 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, and the researchers only knew whether the father had redeemed a prescription for Metformin and not whether the drug was taken as prescribed. Despite this, the evidence is hard to ignore. The study said that 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, while sulfonylurea did show some correlation, but the result was 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 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 still something to be aware of. So 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, a 40% increase still makes them very unlikely. In the context of Metformin in life extension, Dr. Nir Barzali, the chief scientist of the TAME trial, pointed out in an interview with Lifespan.io that it would make the most sense to start taking Metformin around age 50, an age at which many people may not necessarily be worried about the risk of birth defects in offspring. This study appears valuable, but it raises more questions than it answers. The researchers took reasonable steps to get quality data, but there were some limitations that could not be overcome. Ultimately, more studies are needed, and we'll be watching closely for those results, and when they're available, we'll have them for you here. So please subscribe so you don't miss out. I'm Ryan O'Shea, and we'll see you next time on Lifespan News.