Medications
Metformin: Life-Extension Drug
Metformin, a 60-year-old diabetes drug costing pennies per dose, may slow biological aging by activating AMPK, suppressing mTOR, improving mitochondrial function, and reducing inflammation.
01
Quick Facts
| Quick Facts | Details |
|---|---|
| Class | Biguanide / geroprotector (implied) |
| FDA Status | FDA-approved for diabetes; longevity use off-label and unproven |
| Cost | $5-20 per month |
02
The Science: How Metformin Targets Aging Pathways
- AMPK activation — mimics energy-deprived state, autophagy, fat oxidation (evidence: JCI).
- mTORC1 inhibition (evidence: Cell Reports).
- Mitochondrial remodeling (evidence: JCI Insight).
- Cellular senescence & autophagy (evidence: J Advanced Research).
- Epigenetic re-programming (evidence: Diabetes Obesity & Metabolism).
- Anti-inflammatory — IL-6/TNF-α/IL-17 (evidence: Br J Dermatology).
03
What the Research Actually Shows
- FDA-approved diabetes drug; longevity use is off-label and unproven.
- The TAME trial (3,000 participants, six years) is ongoing, with results expected by 2028.
- MILES shows transcriptomic shifts.
04
The Practical Protocol: Dosing
- Start with 500mg with dinner for 1-2 weeks.
- Increase to 500mg twice daily with meals.
- Target 1,500-2,000mg/day, split into divided doses.
- Some cycle off on heavy training days.
05
Lab Monitoring
Reconstructed from the values stated in the source.
| Test | Frequency | Target |
|---|---|---|
| eGFR | Every 6 months | ≥45 mL/min |
| Vitamin B12 | Every 6 months | >400 pg/mL |
| Fasting glucose | Every 3 months | 70-100 mg/dL |
| Lactate | If symptoms | <2 mmol/L |
| CBC | Annually | — |
06
Stacking
- Intermittent fasting
- NAD+ precursors (NR/NMN)
- Senolytics (fisetin/quercetin, alternate)
- Exercise
07
Managing the Risk Profile
- GI discomfort in ~20% of users (nausea, diarrhea, metallic taste); extended-release (XR) reduces this.
- Vitamin B12 depletion.
- Rare lactic acidosis.
- Contraindications include advanced kidney disease.
08
Open Research Questions
Reconstructed from the values stated in the source.
| Research Question | Timeline / Status |
|---|---|
| Healthy-population efficacy | TAME, results by 2028 |
| Optimal longevity dosing | 3-5 years |
| Exercise interaction | Ongoing |
| Genetic testing | 2-3 years |
| Combination protocols | 5+ years |
09
The Investment Case: Bull Case
- 60+ year safety record
- Multi-mechanism action
- $5-20/month
- Mortality benefit signals
- Minimal side effects
- No lifestyle change required
References
- 01How the mechanisms work together — https://pmc.ncbi.nlm.nih.gov/articles/PMC7990352/
- 02Inhibiting aging pathways — https://pmc.ncbi.nlm.nih.gov/articles/PMC5299044/
- 03Anti-inflammatory effects — https://academic.oup.com/bjd/article/189/6/730/7256193
- 04Anti-aging reviews — https://www.thno.org/v12p2722.htm
- 05Harvard Health: is metformin a wonder drug? (adverse events) — https://www.health.harvard.edu/blog/is-metformin-a-wonder-drug-202109222605
- 06Calorie-restriction-mimic mouse study — https://www.nature.com/articles/ncomms3192
This profile is being expanded — additional sections from the source are still being added.
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