1699-P: Effect of Bofanglutide on the Pharmacokinetics of Metformin in Healthy Participants

Introduction and Objective: Bofanglutide is a bi-weekly GLP-1 analog under development for treatment of type 2 diabetes and overweight or obesity. Given the common co-administration of metformin with GLP-1 analogs, it is critical to evaluate the potential pharmacokinetic (PK) interaction between bofanglutide and metformin. Methods: Thirty-two healthy participants (BMI 24-33 kg/m²) received escalating bi-weekly subcutaneous bofanglutide (3, 6, 12 mg, each for 4 weeks) followed by 18 mg for 6 weeks. Metformin (500 mg twice daily for 2.5 days) was administered alone and in combination with bofanglutide (week 6 on 18 mg bofanglutide). Primary PK endpoints were metformin area under the plasma concentration-time curve over the 12-hour dosing interval at steady state (AUC0-tau) and maximum plasma concentration (Cmax). Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. Results: Overall exposure to metformin was comparable with and without bofanglutide, with an AUC0-tau GMR of 0.94 (90% CI: 0.84-1.05), falling within the predefined equivalence range of 0.80-1.25. Metformin Cmax was reduced by approximately 28% during co-administration (GMR 0.72; 90% CI: 0.61-0.84). No serious adverse events occurred; most adverse events were gastrointestinal-related. Conclusion: Bofanglutide had no clinically meaningful effect on overall metformin exposure, indicating that metformin dose adjustment is unnecessary when co-administered with bofanglutide. Disclosure J. Wang: Research Support; Ended; Gan & Lee Pharmaceuticals. J. Zhao: None. L. Zhao: None. T. Xie: None. Y. Li: None. J. Wang: None. X. Yang: None. H. Wu: None. W. Chen: None.