Metformin

Metformin offers clinically proven glucose lowering for overweight adults with type 2 diabetes and can modestly lower the risk of progressing from prediabetes to diabetes, making it a reasonable first-line option for those who need affordable, prescription-grade metabolic support. The evidence supports a 30-plus percent reduction in diabetes incidence in high-risk individuals Knowler et al. 2002 and a 30-plus percent drop in all-cause mortality among newly diagnosed overweight patients UK Prospective Diabetes Study Group 1998. Benefits extend to modest weight loss, improved insulin sensitivity, and a potential longevity signal in observational cohorts, although these signals remain preliminary. Safety concerns focus on gastrointestinal upset, vitamin B12 depletion, and rare lactic acidosis in renal impairment, so regular monitoring is advised. Users seeking hormonal or fertility benefits should note that modest improvements have been observed in polycystic ovary syndrome, but the effect size is modest.

✅ Best for: Adults with type 2 diabetes who need low-cost foundational glucose control and can monitor kidney function and B12. Prediabetes case-by-case when BMI >=30, fasting glucose is high, age is under 60, or prior gestational diabetes raises risk, especially after lifestyle-first work. Insulin-resistant PCOS where ovulation, androgen, and metabolic endpoints matter. Metabolically unhealthy adults where modest weight, glucose, and cardiometabolic risk reduction justify a prescription drug. Longevity-curious users should wait for TAME or use clinician-guided, non-daily, context-specific dosing rather than assuming chronic use is upside-only.

❌ Avoid if: eGFR is below 30; you have acute kidney injury, sepsis, severe dehydration, severe liver disease, active alcohol abuse, decompensated heart failure, hypoxic illness, or an upcoming iodinated contrast procedure that meets FDA hold criteria. Avoid casual daily use if you are a healthy athlete training for hypertrophy, strength, or VO2max, because Konopka 2019 and Walton 2019 show adaptation tradeoffs. Also avoid treating metformin as proven cancer prevention, long-COVID treatment, osteoarthritis therapy, AMD prevention, or healthy-adult anti-aging medicine.