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Background
What do we already know about this topic?
- Type 2 diabetes (T2D) develops as a result of metabolic dysregulation in multiple organ systems, including impaired insulin signaling in skeletal muscle and adipose tissue.
- Tirzepatide is a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
- Although not fully understood, the benefits of GIP receptor engagement are linked to improved adipose tissue health, whole-body energy metabolism, and reduced appetite.1,2
- Several individual metabolites or clusters of related metabolites have emerged that associate with obesity, insulin resistance, and risk for future T2D.
- These include the branched-chain amino acids (BCAA) and related metabolites; a set of triglycerides with short, highly saturated acyl chains; and two metabolites associated with impaired fasting glucose and impaired glucose tolerance.
- Elevations in these metabolites at baseline are predictive for future risk of T2D, whereas reductions are associated with improvement in insulin resistance and weight loss.3-6
How was this study conducted?
- 259 Phase 2b trial participants with T2D were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
- Post hoc exploratory metabolomics and lipidomics analyses were performed on fasting plasma samples collected at baseline, and 4, 12, and 26 weeks.
- The objective was to assess the plasma metabolome changes mediated by tirzepatide.
