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Review
. 2022 Jun;18(1):10-19.
doi: 10.17925/EE.2022.18.1.10. Epub 2022 Jun 16.

Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Shizuka Kaneko  1
Affiliations
Review

Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Shizuka Kaneko. touchREV Endocrinol. 2022 Jun.

Abstract

Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide (GIP) activity or glucagon-like peptide-1 (GLP-1) provide new means for controlling blood glucose levels, body weight, and lipid metabolism. GIP, an incretin, has not been used due to lack of promising action against diabetes. However, recent studies have shown that GIP has an important effect on glucagon and insulin secretion under normoglycaemic conditions. Co-existence of GIP with GLP-1 and glucagon signalling leads to a stronger effect than that of GLP-1 stimulation alone. The development of a GIP/GLP-1R unimolecular dual agonist with affinity for both GIP and GLP-1 receptors is under investigation, and the drug is expected to be clinically available in the near future. Tirzepatide, a GIP/GLP-1R unimolecular dual agonist, regulates metabolism via both peripheral organs and the central nervous system. The SURPASS phase III clinical trials conducted for tirzepatide comprise 10 clinical trials, including five global trials and the global SURPASS-CVOT trial, with >13,000 patients with T2D (ClinicalTrials.gov Identifier: NCT04255433). The clinical application of tirzepatide as a therapy for T2D may provide new insights into diabetic conditions and help clarify the role of GIP in its pathogenesis.

Keywords: Gastric inhibitory polypeptide (GIP); SURPASS; dual agonist; glucagon-like peptide-1 (GLP-1); incretin; tirzepatide; type 2 diabetes mellitus.

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Conflict of interest statement

Disclosures: Shizuka Kaneko reports lecture/consultation fees from Sumitomo Dainippon Pharma Co., Ltd, Novo Nordisk Pharma Ltd, Eli Lilly Japan K.K., AstraZeneca, Boehringer Ingelheim and Mitsubishi Tanabe Pharma Corporation; research support from Novo Nordisk Pharma Ltd, Poxel SA and Eli Lilly Japan K. K and partnership with Novo Nordisk Pharma Ltd.

Figures

Figure 1:
Figure 1:. GIP and GLP-1 secretion acting on receptors in various organs–
Figure 2:
Figure 2:. Function of GIP in insulin and glucagon secretion–
Figure 3:
Figure 3:. Gut activity in patients with T2D undergoing DPP-4 inhibitor therapy, GLP-1R agonist therapy or GIP/GLP-1R dual agonist therapy,
Figure 4:
Figure 4:. Results from the SURPASS clinical trials–
Figure 5:
Figure 5:. Change from baseline in body weight in SURPPASS21,–,–
Figure 6:
Figure 6:. Mild-to-moderate adverse events in SURPASS–
See this image and copyright information in PMC

References

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