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June 7, 2026

2624-P: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orforglipron: A Multiple Dose Titration Study in Chinese Participants with Obesity or Overweight with Weight-Related Comorbidities

H(Hui Liu (33624)PFPing Feng DXDING XUEYING

Key Points

The central aim was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of orforglipron in Chinese participants with obesity or overweight.
Phase 1, randomized, placebo-controlled clinical study (NCT06023095).
Enrolled 24 Chinese participants receiving escalating doses of orforglipron over 16-24 weeks.
Evaluated safety via treatment-emergent adverse events and measured pharmacokinetics and pharmacodynamics parameters.
No serious adverse events or deaths reported; one mild TEAE (diarrhea) led to participant discontinuation.
Significant reductions observed: body weight (-10.21kg), BMI (-3.48kg/m²), waist circumference (-11.66cm), fasting glucose (-0.52mmol/L), and HbA1c (-0.36%).
Pharmacokinetic parameters (AUC[0-24] and Cmax) increased proportionally with doses from 1mg to 36mg.

Abstract

Introduction and Objective: To assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orforglipron, an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1RA), in Chinese participants with obesity or overweight with weight-related comorbidities. Methods: A Phase 1, investigator- and participant-blind, randomized, placebo-controlled clinical study (NCT06023095) enrolled 24 native Chinese participants with stable body weight who received escalating doses of orforglipron over 16 weeks (Cohort 1; up to 12mg) and 24 weeks (Cohort 2; up to 36mg). Safety and tolerability were evaluated by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). PK and PD parameters were measured. Results: 24 Chinese participants, mean (range) age 30.1 (19-48)years, 50.0% females, body mass index (BMI) 32.0 (29.1-34.9)kg/m², waist circumference 98.8 (82.8-117.8)cm, were randomized in 1:1 ratio to orforglipron cohorts 1 or 2 and then in 10:2 ratio to orforglipron cohorts or placebo. In orforglipron group, no SAEs or deaths were reported, and 1 participant discontinued from study due to a TEAE of mild diarrhoea. Most TEAEs were of mild severity, with no severe TEAEs reported. Most frequently reported TEAE was decreased appetite. Events related to gastrointestinal disorders by System Organ Class were most frequently reported. PK profile in Chinese participants aligned with global population. Across 1-36mg dose range, AUC0-24 (42.7-2620ng·h/mL) and Cmax (3.1-159ng/mL) increased in an approximately proportional manner. Substantial reduction from baseline was observed in body weight (-10.21kg), BMI (-3.48kg/m2), waist circumference (-11.66cm), fasting glucose (-0.52mmol/L), and HbA1c (-0.36%). Conclusion: Orforglipron demonstrated consistent safety, tolerability, and PK/PD profiles in Chinese participants with obesity/overweight with weight-related comorbidities, as in global population. Disclosure H. Liu: None. P. Feng: None. D. Xueying: None. S. Zhong: None. X. Du: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. H. Zhuang: Employee; Current; Eli Lilly and Company. X. Ma: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. S. Bhattachar: Employee; Current; Eli Lilly and Company. Y. Yu: None. Funding Eli Lilly and Company

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