TouchREVIEWS in endocrinologyAug 11, 2022

Tirzepatide: A new once-weekly drug that activates two hormones to treat type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 1, 2026

Abstract

The SURPASS phase III clinical trials for tirzepatide involved over 13,000 patients with type 2 diabetes mellitus.

Gastrointestinal hormones, including incretins, are used to manage type 2 diabetes.
has recently shown significant effects on insulin and glucagon secretion under normal blood sugar conditions.
The combination of GIP and signaling may enhance therapeutic effects compared to GLP-1 alone.
Tirzepatide is being developed as a dual agonist targeting both GIP and GLP-1 receptors.
The anticipated clinical availability of tirzepatide could offer new understanding of diabetes and GIP's role in its development.

Simplified

Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide () activity or glucagon-like peptide-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.

Key numbers

90%

HbA1c Achievement Rate

Patients achieving HbA1c levels <7% in SURPASS trials.

6.2–12.9 kg

Weight Reduction

Weight reduction range depending on tirzepatide dosage.

13–27%

Weight Loss Rate

Patients losing 15% or more of body weight.

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Funding

Competing interests

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.

PubMed

Tirzepatide: A new once-weekly drug that activates two hormones to treat type 2 diabetes

Abstract

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Competing interests

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