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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
Relationship between the effects of cisapride on gastric emptying and plasma glucose concentrations in diabetic gastroparesis