Benefits
Metformin is one of the most-studied drugs in medicine, first-line therapy for type 2 diabetes. Its glucose-lowering mechanism is still debated in detail (proposed pathways include AMPK activation, suppression of mitochondrial complex I, and effects on the gut microbiome), but its clinical benefit is extremely well established.
UKPDS 34 (n=753 overweight, newly-diagnosed type 2 diabetics, metformin n=342 vs. conventional diet-based care n=411): metformin produced a 32% risk reduction for diabetes-related endpoints, 42% reduction in diabetes-related death, and 36% reduction in all-cause mortality — and outperformed intensive insulin/sulfonylurea therapy on several of these measures, while causing less weight gain and fewer hypoglycemic episodes. UK Prospective Diabetes Study Group, Lancet, 1998
Side Effects
Most common: gastrointestinal (nausea, diarrhea), generally dose-related and often improving over time. The most serious, well-documented rare risk is lactic acidosis, particularly in patients with kidney impairment — the reason for kidney-function screening before and during use in clinical practice.
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