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Key Takeaways Triple agonist mechanism: Retatrutide is the first medication to activate GIP, GLP-1, and glucagon receptors simultaneously GLP-1 component reduces appetite and slows gastric emptying, the core appetite suppression pathway GIP component improves insulin sensitivity and promotes favorable fat distribution Glucagon component increases energy expenditure through thermogenesis and promotes fat breakdown Weight loss: Phase 2 trials showed up to 24.2% weight loss at 48 weeks, compared to tirzepatide (~22%) and semaglutide (~15%) Investigational status: Not FDA-approved