What do we really know about metformin and ageing?
In people with diabetes, metformin shows clear health benefits. Whether it also slows ageing in healthy people is being investigated by an ongoing study.
Diabetics who use metformin live longer than diabetics on other treatments. That pattern keeps recurring: mortality was around 28% lower than in insulin users and 20% lower than in people on sulphonylureas. Strikingly, metformin-using diabetics even show lower mortality than non-diabetics receiving no treatment at all. This sounds spectacular, but the researchers caution that people who are prescribed metformin may already have better baseline health for all sorts of reasons. The association therefore cannot be straightforwardly reversed into 'metformin saves lives in everyone'.
In animal research the picture is less positive. Metformin did not extend lifespan in mice and fish in a consistent way. Rapamycin, another compound, did so, and to a comparable degree as eating less. Under very specific conditions a positive effect has been seen in worms, but that does not translate directly to humans. This also tempers the expectation that metformin is a universal anti-ageing agent.
From a biological perspective there are good reasons to take metformin seriously as a candidate. It activates an energy sensor in cells, inhibits a growth-signalling pathway involved in accelerated ageing, stimulates the self-clearance of damaged cell components, and reduces low-grade inflammation. All of these processes play a role in how you age. But laboratory and animal findings are not yet proof that this also leads to a longer or healthier life in healthy people.
For healthy, non-diabetic people there is currently no direct evidence that metformin extends lifespan or improves health. The large study designed specifically to test this in non-diabetics has not yet been completed. The safety and optimal dosage in healthy people have also not yet been established, although metformin has been used in people with diabetes for more than sixty years and is considered well tolerated in that setting. Some people respond differently and experience side effects, even if these are generally mild.
In short: metformin is a promising candidate for healthier ageing, but firm confirmation in people without diabetes is still lacking. Wait for the results of that large ongoing study before regarding it as an anti-ageing agent.
This answer draws on three systematic reviews of existing studies and several broad overview articles. The findings in diabetics come from a meta-analysis of 53 studies, but these are observational studies in which people were only followed without any intervention being assigned, which makes cause and effect difficult to prove. The animal data come from two large summaries (one covering 167 articles, one focused specifically on mice and worms) and show no consistent positive effect. The researchers themselves point to high variability between experiments and the possibility that positive results are published more often than negative ones. The MILES study in humans produced preliminary and controversial results. No completed randomised trial in healthy people exists yet; the evidence for lifespan extension in non-diabetics is therefore currently insufficient.
Does metformin help you live longer in good health?
For people with diabetes, metformin has a reasonably well-supported health benefit, but as an anti-ageing agent for healthy people it remains unproven. Wait for the results of that large ongoing study before drawing conclusions.
What are the side effects of metformin?
Metformin causes gastrointestinal complaints such as diarrhoea, nausea and vomiting in a substantial proportion of users. Discuss with your doctor whether the dose can be built up gradually, or consider an alternative if the complaints persist.
What do we know about rapamycin as an anti-ageing agent in humans?
Rapamycin shows early positive signals in humans for the immune system and the skin. But how safe it is in the long term remains unknown, and side effects such as infections and unfavourable blood fats are a real risk. Using it outside a research setting is premature.
Does spermidine actually do anything against ageing?
Spermidine has a well-supported mechanism of action and promising results in animal research, but evidence that a supplement actually works in humans is still lacking. Getting more spermidine through food, such as legumes and wholegrain cereals, is a safe and sensible choice.
How does metformin work in your body?
Metformin lowers blood sugar primarily by causing the liver to produce less new glucose, without the risk of dangerously low blood sugar. Exactly how all the pieces of the mechanism fit together is not yet fully clear.
Does metformin help with weight loss?
Metformin helps with weight loss, but the effect is modest: expect a few kilograms, not a dramatic transformation. Lifestyle changes work better in the short term, but weight loss with metformin remains stable over the long term. Discuss it with your doctor if you want to know whether it suits your situation.