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Dosing Comparison# Survodutide Dosing# Based on Phase 2 trial data and ongoing Phase 3 protocols: Route : Once-weekly subcutaneous injection Dose escalation : Starting dose of 0.25 mg with gradual titration Maintenance doses studied : 2.4 mg, 4.8 mg, and 6.0 mg weekly in Phase 2 Optimal dose : 4.8 mg and 6.0 mg showed greatest efficacy in Phase 2 weight loss trials MASH dosing : Similar dose range evaluated in hepatic endpoints trials Titration rationale : Gradual escalation minimizes GI side effects and allows metabolic adaptation to glucagon receptor activation Tirzepatide Dosing# FDA-approved dosing protocols: Route : Once-weekly subcutaneous injection Starting dose : 2.5 mg weekly for 4 weeks Dose escalation : Increase by 2.5 mg every 4 weeks as tolerated Maintenance doses : 5 mg, 10 mg, or 15 mg weekly Maximum dose : 15 mg weekly Formulation : Prefilled single-dose pens (Mounjaro/Zepbound) and prefilled syringes Storage : Refrigerated

The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions

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however, administration of retatrutide at higher doses significantly reduced circulating FGF21 levels, suggesting that retatrutide efficacy in MASLD is unlikely to be attributable to increased FGF21 levels