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Metformin activates AMPK (AMP-activated protein kinase), reducing hepatic glucose production, improving insulin sensitivity, and triggering autophagy-related pathways similar to caloric restriction. The TAME trial is the first FDA-approved trial to test an anti-aging compound—and metformin is its subject.
Generic metformin is inexpensive, but compounding adds value through custom lower doses for longevity protocols (250–500mg vs standard doses), liquid formulations, combination with berberine or other compounds, and alternative release profiles.
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Metformin has one of the best long-term safety profiles of any medication with over 60 years of use. The TAME trial is testing 1500mg/day in non-diabetic older adults. For longevity use, doses of 500–1000mg daily are typical—lower than standard diabetic doses.
Type 2 diabetes management, longevity and anti-aging protocols, PCOS, pre-diabetes, insulin resistance, off-label weight management.
Diabetes: 500–2000mg daily with meals. Longevity protocol: 500–1000mg daily (often lower than diabetic doses). PCOS: 500–1500mg daily. Start low and titrate to minimize GI side effects.
GI side effects (nausea, diarrhea, stomach upset) most common especially when starting—taking with food and starting low reduces this. Vitamin B12 depletion with long-term use. Lactic acidosis rare but serious. Generally very well tolerated at longevity doses.
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