Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation.

INTRODUCTION: Metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and obstructive sleep apnoea (OSA), are characterized by a complex and interconnected pathophysiological syndrome. These conditions involve insulin resistance, chronic inflammation, and disturbances in energy homeostasis. Typically, they affect multiple organs and require comprehensive treatment. OBJECTIVE: This narrative review examines the multi-organ effects of tirzepatide, a new dual agonist of the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Tirzepatide possesses innovative therapeutic properties and targets multiple metabolic pathways. The review incorporates peer-reviewed sources, including clinical trials, preclinical studies, and specialist reviews. Emphasis is placed on tirzepatide's physiological effects on pancreatic β-cells, adipose tissue, the liver, the gastrointestinal tract, the cardiovascular system, the kidneys, the brain, and gut microbiota. KEY INSIGHTS: Tirzepatide is a dual receptor agonist that increases insulin levels, decreases glucagon levels, slows gastric emptying, and promotes feelings of fullness, contributing to significant weight loss. Recent preclinical studies have shown that tirzepatide can also alter gut microbiota composition, leading to increased Bacteroidetes and decreased Firmicutes. Additionally, tirzepatide has been shown to enhance intestinal barrier integrity. Clinical trial programs, such as SURPASS and SURMOUNT, have demonstrated that tirzepatide provides improved glycemic control and weight loss compared to current treatments. Other benefits include improvements in lipid profiles, reduced hepatic steatosis, and potential protection for the heart and kidneys. CONCLUSION: Tirzepatide is a multi-organ integrator with a therapeutic effect extending beyond glucose regulation. It can influence bowel hormones, improve metabolic parameters, and facilitate communication between different organs, making it a promising treatment for metabolic disorders. However, its broader clinical applications need to be confirmed through additional real-life studies and extended evaluations.