2844-LB: Safety, Tolerability, PK, and PD of Elecoglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Chinese Adults Living with Obesity or Overweight With or Without Type 2 Diabetes

Introduction and Objective: Elecoglipron (ECC5004/AZD5004), an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1RA), is under development for overweight/obesity and type 2 diabetes mellitus (T2DM). This Phase 1b study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in Chinese adults living with obesity or overweight, with or without T2DM, over a 16-week treatment period. Methods: Forty-five participants aged 18-74 years were enrolled. Cohort A (n=24; living with obesity or overweight without T2DM) with BMI 27-35 kg/m2 and weight >=60 kg. Cohort B (n=21; living with obesity or overweight with T2DM) with BMI >=24 kg/m2 and HbA1c 7.0%-10.5%. Participants were randomized 2:1 to once-daily oral elecoglipron or placebo. The treatment regimen consisted of a dose titration phase followed by a maintenance phase for a total of 16 weeks. Results: Of the 45 randomized participants, 44 (97.8%) completed the study. All elecoglipron-treated participants reached the target maintenance dose, except for one in Cohort B. Gastrointestinal were the most frequently reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild in severity; notably, no TEAEs led to treatment discontinuation. No hepatic safety signal was observed and there were no cases of severe hypoglycemia. PD assessments showed that elecoglipron led to clinically meaningful reductions in body weight across both cohorts and HbA1c lowering in Cohort B compared to placebo. Dose-dependent increases in Cmax and AUC were observed across the dose range evaluated. Conclusion: In Chinese participants, elecoglipron demonstrated a safety and tolerability profile consistent with the GLP-1RA class. The observed PD effects on body weight and glycemic parameters support its potential as a promising therapeutic option for patients living with obesity or overweight and T2DM. Disclosure Y. Yu: None. P. Feng: None. W. Cao: Employee; Current; Eccogene. J. Xu: Employee; Current; Eccogene Inc. Q. Li: Employee; Current; Eccogene (Shanghai) Co. Ltd, Shanghai, China. J. Patel: None. J. Zhou: Employee; Current; Eccogene. X. Meng: Employee; Current; AstraZeneca. T. Li: None. X. Zhao: Employee; Current; AstraZeneca. H. Li: Employee; Current; AstraZeneca. B. Zhu: None.