Too TAME?
Originally posted by Dr Maclay on MedBridge Global, May 2025
Do We Really Need to Wait for TAME? Metformin, Prevention, and the Systemic Failure to Invest in Healthspan
The TAME trial—Targeting Aging with Metformin—has captured global attention for a simple yet revolutionary idea: what if we could delay the onset of multiple chronic diseases by targeting aging itself? The study, coordinated by the American Federation for Aging Research (AFAR), proposes that metformin, a well-tolerated and inexpensive drug used for decades in type 2 diabetes, might be repurposed to extend healthspan and prevent age-related decline in healthy older adults.
The trial has full FDA approval, a carefully designed six-year protocol, and academic sites across the US lined up. It plans to enroll 3,000 non-diabetic adults aged 65–79 and measure the time to onset of a range of age-related conditions—cardiovascular events, cancer, cognitive decline, and mortality—making it the first major trial to treat aging itself as a modifiable risk factor. Yet despite all this, TAME has not started. The reason? Funding.
Even with a modest estimated budget of $50–75 million—small change compared to the billions spent annually on end-stage treatments and late-stage diagnostics—the trial remains stuck in pre-launch limbo, waiting for philanthropic or institutional investment. This isn’t just an administrative delay; it’s a telling indictment of how healthcare systems view prevention.
Metformin: Low-Cost, High-Potential, Ignored
Metformin has long been the subject of interest beyond its glucose-lowering effects. Epidemiological and mechanistic studies suggest it reduces oxidative stress, improves mitochondrial efficiency, and may modulate inflammatory and metabolic pathways associated with aging and chronic disease [1–3]. Diabetic patients on metformin have shown lower rates of cancer and all-cause mortality than both untreated diabetics and some non-diabetic populations.
And yet, despite decades of safety data, plausible biological mechanisms, and strong observational evidence, metformin’s application in disease prevention remains largely unexplored in mainstream clinical practice. Why? Because no pharmaceutical company stands to benefit substantially from an off-patent drug, and the regulatory model simply doesn’t know how to handle interventions aimed at aging itself.
In this vacuum, the TAME trial was envisioned as the first formal attempt to change that. Its composite endpoint—multiple age-related diseases—sidesteps the regulatory difficulty of classifying aging as a disease, while still testing the core hypothesis that aging is modifiable. It is, in every sense, a milestone in the evolution of preventive medicine.
But Must We Wait?
For clinicians working on the frontlines of chronic disease—especially those in functional and integrative medicine—the answer is increasingly: no, we cannot afford to wait.
Metformin is not a miracle drug, but it is a rational, mechanistically plausible, and cost-effective intervention for a wide subset of patients. These include:
Middle-aged adults with metabolic syndrome, visceral adiposity, or a family history of chronic disease
Individuals with signs of inflammaging, accelerated epigenetic aging, or impaired glucose metabolism not yet meeting diabetic thresholds
Older adults seeking to extend healthspan, not just lifespan
The risk profile is favourable. The cost is negligible. The theoretical upside is massive. To wait for a six-year trial, which hasn’t even begun enrolling patients, in the context of a rapidly worsening global burden of chronic disease, is a form of passive medical nihilism.
A System That Rewards Sickness
The failure to fund and launch TAME is not just a delay—it’s a symptom of a deeper rot. We live in a medical economy where billions are spent on expensive, late-stage interventions, while simple, scalable prevention is underfunded, ignored, or met with bureaucratic resistance.
There is no better example of this than metformin. If it were a novel agent with patent protection and a $1,000/month price tag, it would likely already have multiple Phase III trials and FDA fast-track designation. But as a generic drug with low profit margins, its potential to reduce disease burden is treated as clinically interesting but economically irrelevant.
Is this the world of Evidence Based Medicine?
The Role of the Practitioner in a Failing System
Functional and integrative medicine practitioners, and those in personalized or preventative health, are uniquely positioned to lead in this space. While large institutions wait for a high-level evidence base to catch up, clinicians can—and should—act with judicious pragmatism.
We must:
Understand the mechanisms and biomarkers relevant to aging and metabolic disease
Apply clinical reasoning and ethical prescribing to select appropriate patients for off-label metformin use
Monitor outcomes and side effects responsibly
Advocate for a paradigm shift in how we think about aging, risk, and intervention timing
TAME is a bold and necessary trial. But the urgent unmet need for prevention doesn’t disappear while we wait. We should support the trial—but we should not confuse the absence of gold-standard evidence with risk.
References
Bannister CA et al. Lancet Diabetes Endocrinol. 2014;2(2):116–124.
Barzilai N et al. Cell Metab. 2016;23(6):1060–1065.
Kulkarni AS et al. Aging Cell. 2020;19(3):e13098.