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The engineering challenge is not just binding affinity but achieving the precise balance that maximizes efficacy while managing the hyperglycemic liability of glucagon (which GIP and GLP-1 agonism must offset)

This negative chronotropic effect of carbachol was accompanied by a negative inotropic effect (Fig

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15 Phase II trials targeting MASH have shown that treatment with SEMA 0.4 mg daily for 72 weeks resulted in more patients with liver fibrosis stage F2/F3 achieving improvement in MASH without progression of liver fibrosis (odds ratio = 6.87, 95% CI = 2.6017.63) compared to placebo