TIRZEPATIDE: NEW POLYPHARMACOLOGY PARADIGM FOR THE TREATMENT OF TYPE2 DIABETES MELLITUS

Abstract

In recent years, multi-target directed ligands (MTDLs) have emerged as an emerging paradigm of polypharmacology for the treatment of diseases with complex and multifactorial etiology, such as type 2 diabetes mellitus (T2DM). Recently, tirzepatide was approved as the first MTDL for the treatment of T2DM, representing a promising therapeutic alternative. In view of this, the present study aimed to review the relevant literature regarding the use of tirzepatide in the treatment of T2DM, exploring the physiological and pathophysiological fundamentals that support its effects on the body. In this proposal, a narrative literature review was conducted, which used books in the areas of physiology, histology, and biochemistry, official documents, drug labels, as well as scientific papers selected from Google Scholar and PubMed. The findings revealed that glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), known as incretins, are among the main hormones involved in the regulation of plasma glucose levels. In the pathophysiology of T2DM, dysfunction of pancreatic β-cells occurs secondary to insulin resistance, which can be influenced by resistance to the stimulatory action of incretins. Consequently, the pancreas reduces its ability to produce sufficient insulin to prevent persistent hyperglycemia, leading to the development of T2DM, with the potential for long-term macro and microvascular complications. In this scenario, tirzepatide has emerged as the first dual agonist of GIP and GLP-1 receptors for the treatment of T2DM, contributing to reducing hyperglycemia, increasing insulin sensitivity, and decreasing dysfunction of pancreatic β-cells. Therefore, it was possible to conclude that tirzepatide, as the first approved MTDL for the treatment of T2DM, offers an innovative approach by mimicking the physiological balance of incretins in the body, resulting in significant therapeutic benefits for patients.