A Randomized-Controlled, Double-Masked Cross-Over Study of a GPR119 Agonist on Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes

• DOI: 10.2337/figshare.28695881.v1
• Publication Date: 2025-04-02T15:44:43Z
• Authors: Anika Bilal; Anna Casu; Fanchao Yi; Tumpa Dutta; Justine M. Mucinski; Gina Mercouffer; Martin C. Marak; Marcus Hompesch; David Kelley; Richard E. Pratley

<p dir="ltr">Activation of GPR119 receptors, expressed on enteroendocrine and pancreatic islet cells, augments glucagon counterregulatory responses to hypoglycemia in pre-clinical models. We hypothesized that MBX-2982, a agonist, would augment experimental participants with type 1 diabetes.<b> </b>To assess this, we designed phase 2a double-masked, cross-over trial 18 (20–60 years) diabetes. Participants were randomized treatment 600 mg MBX-2982 or placebo daily for 14 days two-week washout between treatments. Counterregulatory during hyperinsulinemic-hypoglycemic clamp hormonal mixed meal test (MMT) measured. The maximum response, area under the curve (AUC) incremental AUC not significantly different vs treatment. did alter epinephrine, norepinephrine, polypeptide, free fatty acid, endogenous glucose production compared placebo. However, glucagon-like peptide-1 (GLP-1) response MMT was 17% higher In conclusion, activation improve people Increases GLP-1 are consistent target engagement expected pharmacodynamic from L-cells.</p>