In an era in which life expectancy is lengthening but the years spent in health remain an open challenge, science is starting to look at drugs that we have known for decades with different eyes. Among them is metformin, a simple, inexpensive tablet prescribed every day to millions of people with type 2 diabetes.
The possible protective effects on the cardiovascular system and on some tumors have been studied for some time. Today, however, attention goes even further: can a blood sugar drug influence longevity, to the point of increasing the chances of reaching the age of 90? A new US study suggests that, at least for some women with type 2 diabetes, the answer may be positive.
The study: metformin versus sulfonylureas
The researchers analyzed data from postmenopausal women with type 2 diabetes who had started therapy with metformin or another widely used class of drugs, sulfonylureas.
The result is interesting: those who had started treatment with metformin showed a 30% lower risk of dying before the age of 90 compared to those who had taken sulfonylureas. In technical terms, the hazard ratio was 0.70, a value that indicates a significant reduction in the mortality rate before that age.
We do not speak generically of survival, but of “exceptional longevity”, that is, reaching the age of 90. And it is precisely this change of perspective that makes the study different from other previous research.
The authors explain that they have created the first “target emulation trial” focused on metformin and exceptional longevity in women with type 2 diabetes, observing that the start of therapy with this drug was associated with a greater probability of exceeding that age threshold.
Definitively proving that metformin extends life would require a randomized clinical trial, with people randomly assigned to different drugs and followed for decades, until we see who reaches 90 and who doesn’t. A complex, expensive and very long undertaking.
For this reason the team used an approach called “target trial emulation”, a methodology that allows already existing data to be analyzed as if it were a randomized trial, trying to minimize the distortions typical of observational studies.
The database used is that of the Women’s Health Initiative, a huge American study started in the 1990s which involved over 161,000 women and has continued to monitor their health for more than thirty years. Even today, more than 42,000 participants are active in the follow-up.
From this pool, 438 postmenopausal women who had developed type 2 diabetes and had started treatment exclusively with metformin or sulfonylurea were selected. The researchers corrected the data taking into account age, health conditions and lifestyle, to make the groups as comparable as possible.
Metformin and aging
Metformin is often cited in the field of geroscience, the discipline that studies how to intervene on the biological mechanisms of aging to delay the appearance of multiple chronic diseases at the same time.
According to the authors, the drug acts on several age-related processes: the regulation of insulin signaling, the response to cellular stress and DNA damage mechanisms. Possible benefits have emerged in the laboratory and in animal studies, although results have been mixed in mouse models.
There are also human studies that have not shown a significant reduction in overall mortality compared to placebo in some groups. Precisely for this reason the new work must be read carefully, because it introduces a different angle: instead of asking whether metformin generically reduces the risk of death, it focuses on reaching the age of 90.
However, it is important to state this clearly: the study shows an association, not evidence of cause and effect. The participants were not randomly assigned to the drugs and there was no placebo group. Confounding factors remain possible, such as differences in the severity of diabetes or how doctors choose one therapy over another.
The researchers themselves urge caution, underlining that it cannot be concluded from the data that metformin directly prolongs life. It can be stated, however, that among these women the start of metformin therapy was associated with a greater probability of reaching a very advanced age.
The future: the TAME trial still waiting
The Targeting Aging with Metformin (TAME) project also fits into this line of research, a study proposed to verify whether metformin can delay the onset of various age-related pathologies in the elderly. The trial, however, has not yet started due to lack of funds. In the meantime, the scientific debate continues to grow around so-called gerotherapeutics, drugs capable of acting on the mechanisms of aging and not just on a single disease.
If an economical medicine, already widely used and known, were to also demonstrate an effect on longevity, a completely new scenario would open up in the prevention of chronic diseases. For now it remains a promising lead, which invites caution but also curiosity. Because, sometimes, scientific revolutions start precisely from what we have had under our eyes for years.
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