Searching for Age-Slowing Drugs in the Antidiabetic Portfolio

Data for the ability of metformin to slow aging has researchers looking at other antidiabetic drugs these days, even given that the evidence for metformin to have a meaningful impact on aging in non-diabetic animals is not great, very mixed, and even the human data for a modest addition of a few years in type 2 diabetes patients is most likely not as good as the impact of exercise and control of weight. Still, repurposing drugs to produce modest effects in a different condition has long been a going concern; regulators make it so hard to develop new drugs that it makes economic sense to repurpose existing drugs, even when the likely gains for patients are marginal. The research noted here is par for the course in this respect, finding a gender-specific modest effect on mouse life span for an antidiabetic. Generally, effect sizes in mice for near all metabolism-altering approaches that slow aging are much larger than in humans, so the result here is not all that exciting.

Canagliflozin (Cana), a clinically important anti-diabetes drug, leads to a 14% increase in median lifespan and a 9% increase in the 90th percentile age when given to genetically heterogeneous male mice from 7 months of age, but does not increase lifespan in female mice. A histopathological study was conducted on 22-month-old mice to see if Cana retarded diverse forms of age-dependent pathology. This agent was found to diminish incidence or severity, in male mice only, of cardiomyopathy, glomerulonephropathy, arteriosclerosis, hepatic microvesicular cytoplasmic vacuolation (lipidosis), and adrenal cortical neoplasms. Protection against atrophy of the exocrine pancreas was seen in both males and females.

Thus, the extension of lifespan in Cana-treated male mice, which is likely to reflect host- or tumor-mediated delay in lethal neoplasms, is accompanied by parallel retardation of lesions, in multiple tissues, that seldom if ever lead to death in these mice. Canagliflozin thus can be considered a drug that acts to slow the aging process and should be evaluated for potential protective effects against many other late-life conditions.


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