988-P: MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, Promotes a Dose-Dependent Increase in Gastric Emptying Time

• DOI: 10.2337/db19-988-p
• Publication Date: 2019-06-05T03:45:26Z
• Authors: DARREN ROBERTSON; VICTORIA E. PARKER; PHILIP AMBERY; MARCELLA PETRONE; TAO WANG; TIM HEISE; LEONA PLUM-MOERSCHEL; LUTZ JERMUTUS; BOAZ HIRSHBERG; JURIS J. MEIER
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). GLP-1 and glucagon promote delayed gastric emptying, tolerance has been described. Methods: This exploratory part of a double-blind phase 2a study measured emptying time (GET) in T2DM patients randomized to daily SC (n = 20) or placebo 6) 49 days. Doses were up-titrated fortnightly from 50 300 µg. GET was after 13C-octanoate ingestion via serial breath collection plasma sampling glucose, insulin, Ctrough levels. (t1/2 13C retention decline 50%; tlag when percent excreted dose peaks) at baseline; 15, 29, 43, days; 28 days post-dose. Results: t1/2 significantly prolonged baseline, by 117.2 min (90% CI 56.2, 178.3) v (-42.9 min; 90% -152.0, 66.2; P 0.039), 200 µg 43 dosing. Also, days, prolonged, 46.5 CI, 16.9, 76) (-27.3 -80.0, 25.4; 0.048). Numerical increases seen all levels; increased exposure, as exposure up Lesser delay occurred on day similar but alongside significant reduction glucose AUC -25.3% -28.2, -22.4; < 0.0001). Postprandial insulin levels unchanged despite marked reduction; peak evident. Discussion: promoted dose-dependent increase GET. Although this effect may be evident 50, reduced postprandial observed concurrently indicate insulinotropic effect. unique profile displays characteristics both short- long-acting agonism, suggesting that these effects mediated agonism. Disclosure D. Robertson: Employee; Self; AstraZeneca. Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; V.E. Parker: MedImmune. P. Ambery: M. Petrone: T. Wang: Heise: Advisory Panel; Mylan. Research Support; ADOCIA, Boehringer Ingelheim International GmbH, Dance Biopharm Holdings Inc., Eli Lilly Company, Gan & Lee Pharmaceuticals, Johnson Johnson, MedImmune, Mylan, Nordic Bioscience, Novo Nordisk A/S, Pfizer Poxel, Saniona, Sanofi, Wockhardt, Zealand Pharma A/S. Speaker's Bureau; L. Plum-Moerschel: None. Jermutus: B. Hirshberg: J.J. Meier: AstraZeneca, Merck Sharp Dohme Corp., Sanofi. Funding AstraZeneca