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A suggested mechanism involves prolonged GIPR agonism causing receptor degradation, reducing sustained GIP signalling and, when combined with GLP-1R agonism, causing increased weight loss ( The GLP-1R has itself several LoF variants including R380C, shown by two independent groups to have normal surface expression but reduced affinity for Exenatide (Wootten et al., 2016

Within the framework of fundamental medicine, the approach proposed by integrative physiology can be the only correct way to view the pathological state of an organism, not from the perspective of the presence of a specific disease or multiple comorbid conditions, but as a complex and unified process based on various links of pathogenesis