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Metformin's mechanism: Reduces hepatic glucose production by 20 to 30% through AMPK pathway activation Improves peripheral insulin sensitivity modestly (10 to 15% improvement in muscle glucose uptake) Does not stimulate insulin secretion Does not cause weight gain or hypoglycemia as monotherapy Peak effect at 4 to 6 weeks of consistent dosing Tirzepatide's mechanism: Activates GLP-1 receptors, which stimulate glucose-dependent insulin secretion from pancreatic beta cells Activates GIP receptors, which enhance insulin secretion and may improve beta-cell function Slows gastric emptying, reducing postprandial glucose spikes Suppresses glucagon secretion Produces significant weight loss (15 to 21% at 72 weeks in SURMOUNT trials) Peak glycemic effect at 20 to 24 weeks The mechanisms don't overlap