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TRIUMPH-4 (retatrutide, 68 weeks): Discontinuation due to AEs: 12.2% (9 mg), 18.2% (12 mg) vs 4.0% placebo Key characteristics: Highest GI adverse event rates among the drugs compared here Dysesthesia is a novel safety signal -- abnormal touch sensations affecting up to 21% at the 12 mg dose, not seen in Phase 2

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The downstream effects are dramatic: keratinocyte proliferation and differentiation accelerate, the epidermis compacts and normalizes, melanin transfer is disrupted (fading pigmentation), and dermal fibroblasts are stimulated to produce new collagen while matrix-degrading enzymes (MMPs) are suppressed