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Tirzepatide: Dual GLP-1/GIP Agonist Tirzepatide activates two receptor types simultaneously: GLP-1 (Glucagon-like peptide-1): Slows gastric emptying, reduces appetite, and enhances insulin secretion GIP (Glucose-dependent insulinotropic polypeptide): Improves insulin sensitivity and may have direct effects on fat tissue Retatrutide: Triple GLP-1/GIP/Glucagon Agonist Retatrutide includes everything tirzepatide does, plus a third target: GLP-1: Same appetite suppression and insulin benefits GIP: Same metabolic and insulin sensitizing effects Glucagon receptor: Increases energy expenditure, promotes fat oxidation, and may help preserve lean muscle mass Why Glucagon Matters Glucagon shifts the body toward burning stored fat for energy and increases metabolic rate

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Events (MI, stroke, HF, ESKD and death) were assumed to occur at the mid-point of the cycle