Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders worldwide. Furthermore, cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with T2DM. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the intestine in the presence of food to regulate glucose homeostasis. In addition, These incretin hormones bind to receptors in the pancreas to attenuate rising postprandial glucose levels.

Insulin release and action have to precisely meet the metabolic demand. Hence, the molecular mechanisms involved in the synthesis and release of insulin, as well as the insulin response in tissues must be tightly regulated. In other words, defects in any of the mechanisms involved can lead to a metabolic imbalance that leads to the pathogenesis of T2DM. However, in T2DM, defects in the incretin pathway are common. Therefore, we will introduce a novel dual GIP/GLP-1 RA receptor agonist — Tirzepatide (LY3298176).

Tirzepatide is a dual GIP and GLP-1 receptor agonist.

Tirzepatide is a 39-amino acid synthetic peptide with agonist activity at both the GIP and GLP-1 receptors. Moreover, the structure of Tirzepatide is primarily based on the GIP amino acid sequence and includes a C20 fatty di-acid moiety. Hence, can prolong the duration of action and allow once-weekly subcutaneous administration. Furthermore, Tirzepatide has a greater affinity to GIP relative to GLP-1 receptors expressed on cells. In addition, Tirzepatide shows significantly better efficacy with regard to glucose control and weight loss than Dulaglutide, in vivo.

In summary, Tirzepatide is a hopeful agent for type 2 diabetes mellitus.

Reference:

1. Frias JP, et al. Lancet. 2018 Nov 17;392(10160):2180-2193. 
2. Bucheit J, et al. J Cardiovasc Pharmacol. 2022 Aug 1;80(2):171-179.