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Metformin (Metformin Hydrochloride)

Category: Anti-Aging. Status: FDA-approved (off-label for longevity).

The most prescribed diabetes medication globally, now widely used off-label for longevity. Activates AMPK, mimicking caloric restriction. A staple in telemedicine anti-aging protocols, especially the TAME (Targeting Aging with Metformin) trial framework.

How it works

Activates AMP-activated protein kinase (AMPK), inhibits mitochondrial complex I, reduces hepatic glucose output, and activates autophagy. Mimics the metabolic benefits of caloric restriction.

Key facts

  • Molecular weight: 165.62 Da
  • Half-life: ~6.2 hours
  • Bioavailability: ~50-60% oral
  • Storage: Room temperature.

Dosing overview

  • Typical dose: 500-1000 mg
  • Frequency: 1-2x daily
  • Duration: Ongoing
  • Route: Oral tablet (extended-release preferred)

Protocol notes

  • Longevity protocols typically use ~500-1000 mg/day, well below the max diabetic dose.
  • Start at 500 mg/day (often extended-release) and increase slowly to limit GI side effects.
  • Extended-release is preferred for far better GI tolerance than immediate-release.

Reported benefits

  • AMPK activation
  • Anti-aging cellular effects
  • Cancer risk reduction
  • Cardiovascular protection
  • Blood sugar regulation
  • Longevity support

Possible side effects

  • GI upset
  • Diarrhea
  • B12 depletion
  • Lactic acidosis (rare)
  • Metallic taste

Research

  • Metformin and all-cause mortality (2022): Diabetic patients on metformin showed lower all-cause mortality than non-diabetic controls in large observational studies.
  • TAME trial rationale and biomarkers (2023): Preliminary data suggests metformin reduces epigenetic age acceleration and inflammatory markers in non-diabetic elderly.

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Research and educational reference only. Not medical advice.