2. Academic Validation
  3. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept

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 Sep 6;34(9):1234-1247.e9. doi: 10.1016/j.cmet.2022.07.013.
Tamer Coskun 1,  Shweta Urva 2,  William C Roell 2,  Hongchang Qu 2,  Corina Loghin 2,  Julie S Moyers 2,  Libbey S O'Farrell 2,  Daniel A Briere 2,  Kyle W Sloop 2,  Melissa K Thomas 2,  Valentina Pirro 2,  David B Wainscott 2,  Francis S Willard 2,  Matthew Abernathy 2,  LaRonda Morford 2,  Yu Du 2,  Charles Benson 2,  Ruth E Gimeno 2,  Axel Haupt 2,  Zvonko Milicevic 3
Affiliations

Affiliations

  • 1 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: [email protected].
  • 2 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
  • 3 Eli Lilly and Company, Vienna, Austria.
PMID: 35985340 DOI: 10.1016/j.cmet.2022.07.013
Abstract

With an increasing prevalence of obesity, there is a need for new therapies to improve body weight management and metabolic health. Multireceptor agonists in development may provide approaches to fulfill this unmet medical need. LY3437943 is a novel triple agonist peptide at the Glucagon Receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). In vitro, LY3437943 shows balanced GCGR and GLP-1R activity but more GIPR activity. In obese mice, administration of LY3437943 decreased body weight and improved glycemic control. Body weight loss was augmented by the addition of GCGR-mediated increases in energy expenditure to GIPR- and GLP-1R-driven calorie intake reduction. In a phase 1 single ascending dose study, LY3437943 showed a safety and tolerability profile similar to other incretins. Its pharmacokinetic profile supported once-weekly dosing, and a reduction in body weight persisted up to day 43 after a single dose. These findings warrant further clinical assessment of LY3437943.

Keywords

GIP; GLP-1; energy expenditure; glucagon; glucose control; metabolomics; obesity; triple agonist.

Figures
Products