Tirzepatide is a novel medication approved by the US Food and Drug Administration (FDA) for treating type 2 diabetes mellitus (T2DM). This medication also demonstrates efficacy in weight loss, leading to its off-label use for obesity treatment. Tirzepatide is a dual agonist for the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
Functionally, tirzepatide stimulates insulin release from the pancreas and reduces hyperglycemia. In addition, tirzepatide also increases the levels of adiponectin. The dual agonism ability decreases hyperglycemia significantly more than GLP-1 agonist agents and reduces the patient’s appetite.
In particular, tirzepatide activation of GLP-1 receptors improves glucose-mediated insulin secretion and decreases secretion of glucagon. Tirzepatide activation of GIP receptors augments insulin sensitivity and secretion and thereby helps reinforce the mechanisms regulating blood glucose levels.
Tirzepatide improved markers of insulin sensitivity (IS) and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to weight loss, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.
A 10 mg dose has also been shown to be effective in reducing insulin resistance, with a reduction of around 8% from baseline, measured using HOMA2-IR (computed with fasting insulin). Fasting levels of insulin-like growth factor (IGF) binding proteins such as IGFBP1 and IGFBP2 increased after tirzepatide treatment, increasing insulin sensitivity.
This combination of preference toward GIP receptor and distinct signaling properties at GLP-1 suggest this biased agonism increases insulin secretion. Tirzepatide has been reported to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism, with a maximum increase of 26% from baseline after 26 weeks, at the 10 mg dosage.
This drug aids in controlling blood glucose concentrations which, by definition, are impaired in patients with type 2 diabetes. Tirzepatide is given to patients with type 2 diabetes after meals to stimulate insulin during both phases of its secretion and concurrently suppresses glucagon release, decreasing blood glucose levels. Tirzepatide also increases insulin sensitivity, which aids glucose transport into cells.
