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The triple agonists carry a meaningfully higher tolerability cost than GLP-1 or dual GLP-1/GIP at equivalent efficacy doses - consistent with the GCGR contribution to both efficacy and GI signal

showed that the melanocortin-derived tripeptide KPV produced significant anti-inflammatory effects in DSS colitis and CD45RBhi transfer colitis models two of the most commonly used and accepted IBD research paradigms.1 Critically, the anti-inflammatory effect persisted even in animals with a nonfunctional MC1R receptor, confirming that KPV's action does not depend on melanocortin signaling

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