The TAME clinical trial, still not started, intends to assess the ability of metformin to marginally slow aging in humans. Back at the start of this initiative, it required a long process of negotiation on the part of the trial organizers with the FDA to produce an endpoint that was agreed upon to sufficiently represent aging. To my mind, the TAME trial initiative has already achieved what needs to be achieved: to get the FDA to agree that there is a way to run trials to treat aging. One doesn't actually need to run the trial, and there is in fact little point in running the trial. Metformin is almost certainly a marginal treatment, and attention should be directed instead towards senolytics and other approaches that have much, much better animal data to support their effects on the mechanisms of aging and late life health.
In 2013, Nir Barzilai and two other researchers got a grant from the National Institute on Aging to develop a roadmap to conduct, for the first time in history, a clinical trial that targets aging. They planned to test metformin, a drug that had been approved in the '90s for treating diabetes, and that was shown in epidemiological studies to prevent against conditions like heart attacks, cancer, and Alzheimer's. It also turned out to be very safe, with few, generally mild side effects. And it's dirt cheap: just six cents per dose.
The biggest obstacle they had was the Food and Drug Administration. The federal regulator adheres to a "one disease, one drug" model of approval. And because the agency does not recognize aging as a disease, there's no path forward for a drug to treat it. And even if there was, it's impractical to do a lifespan study - it would take decades and be astronomically expensive. The solution then would be to use biomarkers as a proxy, as researchers have with other treatments. Barzilai's plan was to launch a new kind of gold-standard trial, designed to prove that the onset of multiple chronic diseases, or comorbidities, associated with aging can be delayed by a single drug: metformin. The ambitious effort aimed to track 3,000 elderly people over five years to see if the medicine could hold off cardiovascular disease, cancer, and cognitive decline, along with mortality.
In 2015, he and a group of academics from more than a dozen top-tier universities met with the FDA to get its blessing for their Targeted Aging with Metformin, or TAME, trial. And to many people's surprise, the agency agreed. All that was left was funding it. Because metformin is a generic drug from which no one could make any money, the trial's sponsor wouldn't be a pharmaceutical company, but AFAR. A trial of the scale researchers were proposing would cost between $30 million and $50 million. The National Institutes of Health offered up just a small portion, about $9 million, toward the difficult but important task of screening for the best biomarkers for assessing if the aging process is actually being slowed. The rest of the money, Barzilai was convinced, could be raised from philanthropists. But despite interest from several people - at one point, Barzilai said, the Israeli American businessman Adam Neumann offered to pay for it all, before his WeWork empire evaporated - the required funds never materialized. "Those big billionaires, they want moonshots, they want a scientific achievement that will make people say 'wow'. TAME is not a moonshot. It's not even about scientific achievement really, it's more about political achievement. Metformin is a tool to get aging as an indication."
Link: https://www.statnews...ial-overlooked/
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