Fight Aging!

The Targeting Aging with Metformin (TAME) clinical trial has been a feature of the divide between regulators, researchers, and industry in the matter of treating aging as a medical condition for as about as long as the longevity industry has existed. Regulators such as the FDA do not consider aging to be a disease, and they only approve treatments for specific diseases, largely using the World Health Organization's International Classification of Diseases as the basis for what is and is not a disease. The TAME trial came into being as a way to convince the FDA to approve a treatment on the basis of endpoints that approximated aging, rather than a disease.

In that sense the heavy lifting has been accomplished: the FDA indeed agreed with the TAME trial design, and so in principle anyone else with deep pockets could now adopt the same approach if they wanted to stand behind a treatment for aging. The biotech industry and those who fund it are highly conservative, however. Companies working on therapies that can in principle slow or reverse aspects of aging have all chosen to pick one or more specific age-related diseases, and quietly plan for off-label use following approval, as it is unlikely that they could otherwise have convinced investors to back their clinical and regulatory development.

As today's popular science article notes, the TAME trial remains incompletely funded. This, I suspect is the case in large part because metformin is a poor choice of treatment. It was selected because it is so very widely used, for so long, and with such an abundance of safety data, that the FDA could not possibly object on those grounds. Hindsight is 20/20, but rapamycin would have been a much better choice. The evidence for metformin to slow aging is not great. The animal data is mixed, to say the least, and the human data from studies of type 2 diabetes patients has a great many issues. Rapamycin more clearly slows aging, the animal data is robust, and human evidence shows minimal to no side-effects at the dose for anti-aging use. Still, here we are: it remains unclear as to whether the TAME trial will be completed, or be overtaken by events. The evolution of regulation with regards to the treatment of aging will likely shift to a battle over widespread off-label use as the first longevity industry therapies are approved for specific disease.

A cheap drug may slow down aging. A study will determine if it works

Metformin was first used to treat diabetes in the 1950s in France. The FDA approved metformin for the treatment of type 2 diabetes in the U.S. in the 1990s. Since then, researchers have documented several surprises, including a reduced risk of cancer. As promising as this sounds, most of the evidence is observational, pointing only to an association between metformin and the reduced risk. The evidence stops short of proving cause and effect. Also, it's unknown if the benefits documented in people with diabetes will also reduce the risk of age-related diseases in healthy, older adults.

Back in 2015, a bunch of aging researchers began pushing for a clinical trial. "A bunch of us went to the FDA to ask them to approve a trial for metformin, and the agency was receptive. If you could help prevent multiple problems at the same time, like we think metformin may do, then that's almost the ultimate in preventative medicine." The aim is to enroll 3,000 people between the ages of 65 and 79 for a six-year trial. But it's been slow going to get it funded. "The main obstacle with funding this study is that metformin is a generic drug, so no pharmaceutical company is standing to make money."

Researchers have turned to philanthropists and foundations, and has some pledges. The National Institute on Aging, part of the National Institutes of Health, set aside about $5 million for the research, but that's not enough to pay for the study which is estimated to cost between $45 and $70 million. The frustration over the lack of funding is that if the trial points to protective effects, millions of people could benefit. Currently the FDA doesn't recognize aging as a disease to treat, but the researchers hope this would usher in a paradigm shift - from treating each age-related medical condition separately, to treating these conditions together, by targeting aging itself.