Do diabetes pills (SGLT2 inhibitors) also work against ageing?
For people with heart or kidney problems, large trials show that SGLT2 inhibitors clearly do more than lower blood sugar alone. As an anti-ageing pill for healthy individuals, it is still too early for a practical recommendation.
SGLT2 inhibitors (such as empagliflozin and dapagliflozin) are diabetes pills that prompt the kidneys to shed excess sugar through the urine. Several large trials show that, in people with and without diabetes alike, they substantially reduce the risk of heart failure, kidney failure and all-cause mortality. That is robust, direct evidence that they do more than simply lower blood sugar1,2,3.
At the cellular level, SGLT2 inhibitors do something similar to caloric restriction, a well-known way of slowing ageing. They activate energy sensors and suppress growth sensors, enabling cells to clear and recycle damaged components more effectively. For now, however, this comes largely from animal and laboratory research. Direct confirmation in humans is still mostly lacking1,2,3,4.
SGLT2 inhibitors also appear to suppress 'inflammaging': the smouldering low-grade inflammation that increases over the years and contributes to cardiovascular disease and dementia. Both animal studies and human studies show lower inflammatory markers. Those studies were simply not designed specifically as ageing research2,1.
A clever genetic study found a link between lifelong SGLT2 inhibition and a longer lifespan (on average 6.2 years for the father per standard deviation decrease in average blood sugar) and better cognition. That sounds impressive, but this is not a direct measurement in people who are taking the pill. The method has serious limitations and the findings are far from proven5.
In a large Taiwanese study of more than 280,000 patients, SGLT2 inhibitors protected the kidneys better than another popular diabetes pill, even in frail older adults. The risk of dialysis or kidney transplant was 2.4 to 3.9 times higher with the other pill6. Two further caveats: there is almost no research on how SGLT2 inhibitors interact with exercise, whereas some anti-ageing agents can counteract the benefits of physical activity7. And a review article promoting supplements as boosters of SGLT2 inhibitors comes from authors with financial interests in supplement companies; the underlying evidence is weak8.
The claims are based on large clinical trials (cardiovascular and kidney outcomes), one large observational study (Taiwan, n=280,000+), Mendelian randomisation, mechanistic/preclinical studies, and a review with a potential conflict of interest. No randomised trials have used lifespan or biological ageing as a primary endpoint. Meta-analyses were not provided as a direct source; however, large trials were included.