J Korean Diabetes.  2024 Jun;25(2):76-81. 10.4093/jkd.2024.25.2.76.

GLP-1/GIP Receptor Agonists: Mechanism of Action of Tirzepatide

• Oh TJ

• KMID: 2556757
• DOI: http://doi.org/10.4093/jkd.2024.25.2.76

Abstract

Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated remarkable effectiveness in lowering glucose levels and reducing weight in the SURPASS and SURMOUNT trials. However, its mechanism of action in vivo remains incompletely understood. Although pancreatic beta cell express both GLP-1 and GIP receptors, the insulinotropic effect of GIP is attenuated under hyperglycemic conditions. Tirzepatide may enhance the role of GLP-1 and potentially restore the insulinotropic effect of GIP. Furthermore, the expression of GIP receptors in adipose tissue suggests that tirzepatide may directly impact adipose tissue function, contributing to its ability to regulate hyperglycemia and obesity. Despite these insights, the precise mechanism of action of tirzepatide remains unknown, as its unprecedented effects cannot be solely attributed to reduced food intake. Further research is warranted to fully comprehend the therapeutic potential of this agent.

Keyword

Diabetes mellitus; Glucagon-like peptide 1; Incretins; Obesity

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