Aims: Some studies have shown that in type 2 diabetic patients the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) is compromised but can be partially restored if glucose is lowered. Renewed interest for this phenomenon has been expressed in the context of the new dual GIP-GLP-1 (glucagon-like peptide-1) receptor agonists, which have shown greater efficacy of this drug class compared with single GLP-1 receptor agonists, including on insulin secretion. However, contrasting evidence has been reported on the recovery of GIP action with glucose lowering. In our study, we reconsider all publications relevant for the problem and analyze the results using a uniform methodology.
Data synthesis: We show that, while some contradictions might be explained by heterogeneous analysis methods, it is possible to interpret all the available data coherently and conclude that the effect of glucose lowering is relevant only when glucose concentration is virtually normalized.
Conclusions: While a significant restoration of GIP action may not occur with some traditional diabetes treatments, GIP action improvement might become relevant when glucose is virtually normalized and could explain part of the success of the double GIP-GLP-1 receptor agonists.
Keywords: GIP receptor; GIP receptor Agonists; Glucose-dependent insulinotropic polypeptide; Insulin secretion; Type 2 diabetes.
Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.