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This might arise early in the pathogenesis of T2DM, as one of many risk factors contributing to the initial onset of hyperglycaemia in susceptible individuals, or later, as a consequence of already existing metabolic changes causing increased DPP-4 activity and further exacerbating the deterioration of glycaemic control
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34,35 However, the controversy surrounding the possible benefits of GIPR agonism stems from two main observations: its impaired insulinotropic effects, 36,37 and the prevention of weight gain by suppression of endogenous GIP-induced adipogenesis, 38,39 However, these seemingly discouraging observations have been questioned by the finding of the central anorexic effects of GIP, 40–42 and benefits of the GLP-1R/GIPR dual agonist LY3298176 (tirzepatide) in diabetic and overweight individuals
