Researchers and advocates have been trying for some years to launch the TAME trial to assess the effects of metformin on aging in humans. This is not with the hope of producing meaningful effects on the progression of aging. Metformin has a small effect size, being one of the less effective interventions that upregulates cellular stress responses, a strategy that in and of itself is weak in long-lived species such as our own. The goal is to push the FDA into accepting clinical trials that target mechanisms of aging rather than a specific named age-related condition. Metformin was chosen because its safety profile, widespread use, and length of time as an approved drug make it hard for the FDA to object on technical grounds.
I view this whole exercise as an example of the harmful distorting effect of regulation on progress in medicine: years of effort and tens of millions of dollars will be wasted on an exercise that everyone involved knows will produce only tiny gains in health and longevity at the end of the day. In a sane world, those resources could have gone towards far more effective projects, those with a much greater expectation of extending healthy human life span and producing rejuvenation in the old.
After closing the final $40m of its required $75m budget with a donation from a private source, the first drug trial directly targeting aging is set to begin at the end of this year, lead researcher Dr Nir Barzilai has revealed. Back in 2015, when his revolutionary anti-aging trial TAME finally received FDA approval, it would have been forgivable to think that Dr Barzilai had, at last, got past the hard part. But TAME went into financial limbo, with many wondering if it would ever be able to escape. His trial TAME (Targeting Aging with Metformin) had been stalled for four years while he and his colleagues engaged in funding negotiations with the US NIH (National Institute of Health). "It was down to their conservative approach over there. They really didn't understand what we were trying to achieve."
For those accustomed to judging the success of a drug trial's funding acquisition by the safety and efficacy record of its drug, TAME's funding difficulties could look confusing. Safely used and widely prescribed, the trial's antidiabetic drug, metformin, has been US FDA approved since 1994. Its use in medical practice extends back into the Middle Ages, where it was extracted from the French lilac and later in France from the 1950s onwards, when the isolated compound was first successfully administered to diabetic patients.
But it is much more the trial structure, rather than the drug itself, that is on trial. Instead of following a traditional structure given to FDA approved trials (that look for a single disease endpoint) TAME has a composite primary endpoint - of stroke, heart failure, dementia, myocardial infarction, cancer, and death. Rather than attempting to cure one endpoint, it will look to delay the onset of any endpoint, extending the years in which subjects remain in good health - their healthspan.
In a retrospective 2014 analysis of 78,000 adult type 2 diabetics in their 60s, those who took metformin lived longer, on average, than healthy controls of the same age. This has led a growing body of doctors beginning to prescribe the drug off-label, so that their patients may benefit from its purported anti-aging effects. Such widespread speculation demands deeper scientific investigation. It is TAME's composite primary endpoint, created with the cooperation of the FDA, that excites Barzilai and his colleagues. They hope that Big Pharma will use it to develop drugs with even more powerful anti-aging effects.