- Urva et al 81st Annual Scientific Sessions of the American Diabetes Association. Jun 2021
- Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.e9.
- EMA/CHMP review (EMA, 2017)
Background
What do we already know about this topic?
- Novel LY3437943, a single peptide engineered from a gastric inhibitory polypeptide (GIP) peptide backbone, has triple-agonist activity for GIP, glucagon-like peptide 1 (GLP-1), and glucagon receptors. This C20 di-acid acylated peptide has high albumin binding, which enables prolonged activity and once weekly dosing.
- In preclinical studies LY3437943 has been shown to cause loss of body weight by reducing food intake and increasing energy expenditure (EE) in diet-induced obese (DIO) mice; this weight loss is greater than that observed with dual GIP/GLP-1 receptor agonist.2
- LY3437943 has also been shown to result in dose-dependent weight loss after a single subcutaneous (SC) dose in health human patients.2
How was this study conducted?
- The study was designed as a 12-week Phase 1, multi-centre, double-blinded, placebo-controlled, randomised, multiple-ascending dose study in patients with type 2 diabetes (T2D) being treated with metformin, at 4 centres in the United States.
- This trial sought to primarily assess the safety and tolerability of QW LY3437943 after 12 weeks of treatment in patients with T2D, and secondarily to characterise the pharmacokinetic (PK) profile and conduct pharmacodynamic (PD) assessments.
- A small group of patients administered dulaglutide was included in each cohort as a positive control to better assess the effect of LY3437943.
