A low-cost oral medication with a seventy-year record in blood sugar management. The strongest evidence stays there: lower blood sugar, better response to insulin, delayed onset of diabetes. Broader slowing of aging remains unresolved — corrected human data run against it, monkey data renew the case. Documented costs: digestive upset, vitamin B12 depletion, dampened gains from training. (Full Review)
| Marker | Target | Why |
|---|---|---|
| eGFR | >90 mL/min/1.73 m² | Governs dosing and lactic acidosis risk |
| Serum vitamin B12 | 500–1,100 pg/mL | Detects the drug's most common nutritional depletion |
| Methylmalonic acid | <0.27 µmol/L | Confirms functional B12 status when serum B12 is borderline |
| Homocysteine | <9 µmol/L | Reflects combined B12 and folate adequacy |
| HbA1c | 4.9–5.4% | Primary measure of the drug's glycemic effect |
| Fasting glucose | 75–86 mg/dL | Reflects overnight hepatic glucose output, metformin's main target |
| Fasting insulin | 2–5 µIU/mL | The earliest marker of the insulin resistance metformin addresses |
| HOMA-IR | <1.0 | Single summary index of insulin resistance and the strongest predictor of who benefits |
| High-sensitivity C-reactive protein | <0.5 mg/L | Tracks the chronic low-grade inflammation metformin is proposed to reduce |
| Mean corpuscular volume | 82–89 fL | Early signal of B12 or folate depletion before symptoms appear |
| Alanine aminotransferase | <20 U/L (men), <17 U/L (women) | Screens for the rare hepatic reaction and tracks fatty liver, a common co-indication |
| Thyroid-stimulating hormone | 0.5–2.0 mIU/L | Detects the drug's suppressive effect in people on thyroid replacement |
| Venous lactate | <1.6 mmol/L | Investigated only if symptoms suggest acidosis |
Cadence: Kidney function and metabolic panel at 3 and 6 months, then annually — every 3 months below eGFR 45 mL/min/1.73 m² or with renally active co-medications. HbA1c, fasting insulin, HOMA-IR at 3 months, then every 6–12 months. Vitamin B12 at 12 months, then annually, with methylmalonic acid whenever serum B12 is below 400 pg/mL. Complete blood count annually. Cardiorespiratory fitness and body composition at baseline, then every 6–12 months.