Metformin for Longevity? Joseph Raffaele Explains Why Context Matters
Joseph Raffaele, Physician-Scientist in Longevity Medicine, CEO of PhysioAge LLC, posted on LinkedIn:
”Metformin was supposed to be the longevity drug.
The data isn’t as clean as we hoped.
The longevity space has long hailed metformin as a promising geroprotector. The TAME trial (Targeting Aging with Metformin) aimed to prove it could delay multiple age-related diseases.
But recent evidence suggests the story is more complicated.
What we know:
- Metformin activates AMPK, improving insulin sensitivity and reducing inflammation
- Observational studies showed diabetics on metformin lived longer than expected
- Animal studies demonstrated lifespan extension in certain models
What we’re learning:
A recent Cell Metabolism study found that in non-diabetic individuals engaged in regular exercise, metformin:
- Blunted mitochondrial adaptations to training
- Reduced VO₂ max gains by 30% compared to placebo
- Impaired muscle protein synthesis responses
Another 2023 study showed metformin reduced NAD+ levels in skeletal muscle, potentially accelerating some aspects of metabolic aging.
My clinical POV?
Metformin isn’t inherently “good” or “bad,” it’s context-dependent.
Who it can benefit: Pre-diabetic or insulin-resistant patients, sedentary individuals at high risk for type 2 diabetes, or those with strong family history of diabetes or metabolic syndrome.
Who should think twice: Highly active individuals optimizing athletic performance, lean or metabolically healthy people with low insulin resistance, and those already struggling with low NAD+ or mitochondrial function.
This is why individualised testing and monitoring matter more than headlines.
Follow Joseph Raffaele for evidence-based perspectives on what’s actually working in longevity medicine beyond the hype, grounded in 25 years of clinical practice.
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