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Meta-analysis of these studies demonstrated (Figure 4) that there was no significant difference in the mean changes (follow-up from baseline) between groups (SMD, 0.006
The evidence does not establish a complete receptor-to-effector pathway for the reported adipocyte effects
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In a mouse model of diet-induced NASH, Notch signaling in hepatocytes induces osteopontin secretion, paracrine HSC activation and hepatic fibrosis, which are abrogated by Notch inhibition (132)
This Gs-biased profile may contribute to sustained receptor signaling with less desensitization, though the clinical implications of signaling bias in GLP-1 therapeutics remain an area of active investigation
