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- W4385663314 startingPage "3079" @default.
- W4385663314 abstract "Tirzepatide is a unimolecular co-agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors recently approved for the treatment of type 2 diabetes by the US Food and Drug Administration and the European Medicine Agency. Tirzepatide treatment results in an unprecedented improvement of glycaemic control and lowering of body weight, but the contribution of the GIP receptor-activating component of tirzepatide to these effects is uncertain. In this review, we present the current knowledge about the physiological roles of the incretin hormones GLP-1 and GIP, their receptors, and previous results of co-targeting the two incretin hormone receptors in humans. We also analyse the molecular pharmacological, preclinical and clinical effects of tirzepatide to discuss the role of GIP receptor activation for the clinical effects of tirzepatide. Based on the available literature on the combination of GLP-1 and GIP receptor activation, tirzepatide does not seem to have a classical co-activating mode of action in humans. Rather, in vitro studies of the human GLP-1 and GIP receptors reveal a biased GLP-1 receptor activation profile and GIP receptor downregulation. Therefore, we propose three hypotheses for the mode of action of tirzepatide, which can be addressed in future, elaborate clinical trials." @default.
- W4385663314 created "2023-08-09" @default.
- W4385663314 creator A5002832666 @default.
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- W4385663314 creator A5045349000 @default.
- W4385663314 creator A5079352451 @default.
- W4385663314 creator A5085434984 @default.
- W4385663314 date "2023-08-08" @default.
- W4385663314 modified "2023-10-17" @default.
- W4385663314 title "The importance of glucose‐dependent insulinotropic polypeptide receptor activation for the effects of tirzepatide" @default.
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