Gabriela Anglart, Laura Janik, Katarzyna Dettlaff

Tirzepatide – a new analogue of incretin hormones
2023-10-20

Type 2 diabetes and obesity are civilization diseases with an ever-increasing number of cases. Obesity, which is an excessive accumulation of visceral body fat, is considered to be one of the main causes of type 2 diabetes. It promotes the accumulation of fatty acids in muscles, liver, heart, and blood vessels and can lead to insulin resistance. The development of type 2 diabetes and obesity may be associated with an inappropriate lifestyle or chronic, autoimmune inflammatory process induced by glucotoxicity and lipotoxicity.

In type 2 diabetes, drugs are administered gradually, depending on the progression of the disease. Currently, glucagon-like peptide-1 analogues, such as liraglutide or semaglutide, are used more often in effective treatment. One of the newest drugs is tirzepatide, approved in 2022 - the first glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) dual analogue. GIP and GLP-1 influence pancreatic  cells in both complementary and synchronized manner. GLP-1, a product of the glucagon gene, stimulates insulin secretion depending on current glycemia. Thanks to this process and other mechanisms, GLP-1 affects the regulation of blood glucose level. It also inhibits glucagon secretion by pancreatic  cells. GIP stimulates insulin secretion by pancreatic  cells depending on glucose level but does not affect glucagon secretion. Thanks to such cooperation, GIP hormone can have benefits beyond its original, incretin role. These benefits include increasing insulin sensitivity as well as maintaining proper lipids level.

This article presents the structure of tirzepatide, its mechanism of action, an overview of clinical trial results, and its safety assessment. Clinical trial results have shown a very beneficial effect of tirzepatide on glycemic control and bodyweight reduction. In all performed phase III studies, tirzepatide was more effective than any other drug used in any reference group (including semaglutide). Double agonism of incretin hormones seems to be a promising therapeutic concept.

Keywords: type 2 diabetes, obesity, incretin hormones, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide.

© Farm Pol, 2023, 79(5): 289–296