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Retatrutide vs tirzepatide vs semaglutide Category Receptor targets Retatrutide GLP-1 + GIP + Glucagon (triple) Tirzepatide GLP-1 + GIP (dual) Semaglutide GLP-1 only (single) Category Half-life Retatrutide ~6 days Tirzepatide ~5 days Semaglutide ~7 days Category Dose frequency Retatrutide Once weekly Tirzepatide Once weekly Semaglutide Once weekly Category Max studied dose Retatrutide 12 mg/week Tirzepatide 15 mg/week Semaglutide 2.4 mg/week Category Peak weight loss in trials Retatrutide -28.7% at 68 weeks (Phase 3 TRIUMPH-4) Tirzepatide -22.5% at 72 weeks (SURMOUNT-1) Semaglutide -15.8% at 68 weeks (STEP-1) Category FDA status (June 2026) Retatrutide Investigational, Phase 3 Tirzepatide Approved (obesity + T2D) Semaglutide Approved (obesity + T2D) Category Liver fat Retatrutide Up to 82% reduction (Phase 2 substudy) Tirzepatide Significant reduction Semaglutide Moderate reduction Category Unique angle Retatrutide Triple agonism may raise energy expenditure via glucagon pathway Tirzepatide Dual agonism balances effect and tolerability Semaglutide Longest clinical track record

There is also a specific biological reason the systemic route attracted attention

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Our sophisticated defense mechanism, the immune system, protects us from harmful intruders such as viruses and bacteria