Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes

Tirzepatide is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clinical outcomes beyond those achieved by a selective GLP-1 receptor agonist like dulaglutide Improved glycemic control was associated with lower circulating triglycerides and lipoprotein markers and improved markers of beta-cell function and insulin resistance (IR) In this Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks. Post hoc exploratory metabolomics and lipidomics analyses were performed. At 26 weeks, tirzepatide modulated a cluster of metabolites and lipids associated with IR, and obesity. The decrease in metabolites like branched-chain amino acids, glutamates, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate compared to baseline and placebo. were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, HOMA 2-IR indices, and proinsulin levels. Similarly, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo The study thus concluded that Tirzepatide reduces body weight and improves glycemic control and uniquely modulates metabolites associated with T2D risk and metabolic dysregulation in a direction consistent with improved metabolic health. Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.