Compound Physician required

Metformin

500 to 2,000 mg daily. Old drug, long track record, possible longevity signal.

Approved Verified 27 August 2026

What it does

Decades of use in type 2 diabetes, plus observational longevity signals in non-diabetic populations. Most useful where insulin resistance is present; the case in metabolically healthy people is weaker, and it may blunt some endurance adaptations.

Inhibits hepatic gluconeogenesis primarily through AMPK activation and complex I inhibition, with downstream effects on insulin sensitivity and lipid metabolism.

  • insulin sensitivity
  • HbA1c
  • hepatic glucose output

What the evidence shows

Overall evidence strength: Moderate certainty

Who it's for, who should skip

Insulin resistance or metabolic risk. In already-insulin-sensitive individuals the case is weaker, and the exercise-adaptation tradeoff matters more.

Running it

Form
oral
Dose
500–2,000 mg · daily
Titration
titrate to tolerance; extended-release often better tolerated

Measuring it

Retest HbA1c — Quarterly while titrating or not at goal, every 6 months once stable — monitor B12 with long-term use..

  • HbA1c baseline
  • HbA1c quarterly
  • Fasting glucose baseline
  • Fasting glucose on cycle

Safety

  • GI effects, often transient common
  • vitamin B12 depletion with long-term use
  • lactic acidosis rare

Stacking & alternatives

Pair it with

  • vitamin B12 — Long-term metformin depletes vitamin B12; monitor and supplement as needed. recommended · ongoing

Access & cost

Prescription or clinician order — typically via primary care or endocrinology.

Last reviewed 27 August 2026. Regulatory status verified 27 August 2026.