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49 However, an interim analysis at 72 weeks of a phase 3 trial of semaglutide 2.4 mg once weekly for MASH showed histological improvements, including resolution of fibrosis, reduction of liver fibrosis and resolution of steatohepatitis in a significant number of patients

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IGF1 combines with IGF1R, activates the Ras/MEK signaling pathway, and promotes the expression of transcription factors, such as E2F, Foxo3a, and ELK (Reuter et al., 2010), thereby promoting cell proliferation

This directly complicates patient screening and enrollment, leads to substantially lower overall expected efficacy compared with patients harboring upstream genetic defects (such as POMC deficiency) [56] , and results in a low statistical success rate in large-scale trials

This is for several reasons