- Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med 2017;23(7):804–14.
- Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab 2018;18:3–14.
- Frias JP, Nauck MA, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet 2018;392(10160):2180–93.
Background
What do we already know about this topic?
- Impairment in insulin production from pancreatic beta cells and in insulin action both contribute to hyperglycaemia in people with type 2 diabetes (T2D).1
- Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1RA).2
- It has previously demonstrated demonstrated substantially greater glucose control and weight loss compared with the selective GLP-1RA dulaglutide.3
How was this study conducted?
- This was a post hoc analysis of data from a Phase 2b study, in which subjects were randomised to tirzepatide (1 mg, 5 mg, 10 mg, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks.
- The analysis used exploratory biomarkers from fasting blood samples to see how tirzepatide induces glucose control.
- The biomarkers examined included intact proinsulin, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-2.
- Homeostatic model assessment indices for beta-cell function (HOMA2-B) or insulin resistance (HOMA2-IR) were computed with fasting glucose and insulin or C-peptide levels.
