Metformin & Longevity: Where the Science Stands Today
Metformin has quietly become the most discussed pharmaceutical candidate in longevity medicine. The ongoing TAME trial may finally tell us whether its promise extends beyond diabetes.
The News
The Targeting Aging with Metformin (TAME) trial continues enrollment, aiming to determine whether metformin can delay the onset of age-related diseases in non-diabetic individuals.
My Take
Metformin is one of the most extensively studied drugs in longevity research. Observational data suggests diabetics on metformin have lower mortality than expected — in some analyses, even lower than non-diabetics.
Animal studies demonstrate modest lifespan extension, and decades of clinical use confirm that metformin is generally safe, inexpensive, and well tolerated. These factors make it uniquely positioned among potential longevity drugs.
The Mechanism
Metformin’s effects extend beyond glucose lowering. Key mechanisms include:
- Activation of AMPK, the cell’s primary energy sensor
- Improved insulin sensitivity
- Reduction of hepatic glucose production
- Induction of mild mitochondrial stress (hormesis)
- Anti-inflammatory effects
Current Evidence in Non-Diabetics
Data in healthy populations remains limited. Small studies suggest possible improvements in healthspan markers, reduced cancer incidence in certain groups, better cardiovascular risk profiles, and potential cognitive protection.
However, no definitive evidence yet shows that metformin extends lifespan in healthy humans — precisely what the TAME trial aims to clarify.
My Clinical Experience
I have prescribed metformin off-label for longevity in select patients — most commonly those with prediabetes, metabolic syndrome, or strong family history of type 2 diabetes who have not responded adequately to lifestyle changes.
Typical dosing ranges from 500–1000 mg daily, starting low to minimize gastrointestinal side effects.
Key Considerations
- May impair vitamin B12 absorption — levels should be monitored
- Gastrointestinal symptoms are common initially
- Potential blunting of some exercise adaptations (still debated)
- Rare risk of lactic acidosis, especially with kidney dysfunction
Who Might Benefit
- Individuals with insulin resistance or prediabetes
- Strong family history of type 2 diabetes
- Those struggling with metabolic optimization despite lifestyle efforts
- People seeking a low-risk, low-cost longevity intervention