Metformin is the world's most prescribed diabetes drug — ADA 2026 confirms it first-line. This complete guide covers the triple AMPK mechanism, why ER is now preferred over IR (ADA 2026), the contrast dye hold rule millions miss, B12 depletion in 7–30% of long-term users, honest weight loss data (2–5 lbs — not a weight loss drug), lactic acidosis black box in accurate context, and the TAME longevity trial explained.