643-P: A Model-Based Evaluation of Glycemic and Weight Changes When Switching from Semaglutide to Additional Doses of Dulaglutide

Abstract

Dulaglutide 3.0 and 4.5 mg subcutaneous (SC) once weekly (QW) doses are approved for glycemic control in patients with type 2 diabetes (T2D). Using pharmacokinetic/pharmacodynamic models built from and validated with published data from SUSTAIN 1 to 10 trials for SC semaglutide and patient-level data from AWARD-11 for dulaglutide, simulations were used to predict the glycated hemoglobin (A1c) and bodyweight effects of switching from semaglutide 0.5 mg or 1.0 mg QW to 3.0 mg or 4.5 mg dulaglutide. Simulations of 100 trials with 100 virtual patients with T2D per scenario were generated by a sampling with replacement method from the AWARD-11 study dataset, which compared 3.0 and 4.5 mg dulaglutide doses to 1.5 mg as an add-on to metformin in 1842 patients with T2D with a mean baseline age of 57 years, weight of 96 kg and A1c of 8.6%. In the simulations, semaglutide was initiated at 0.25 mg for 4 weeks per approved label, and 52-week time-course predictions were conducted for changes from baseline (CFB) in mean A1c and body weight for semaglutide 0.5 mg QW or 1.0 mg QW for 26 weeks, followed by a switch to dulaglutide 0.75 mg QW or 1.5 mg QW and dose-escalated every 4 weeks to 3.0 mg QW or 4.5 mg QW, for the remaining 26 weeks. At 26 weeks, model-predicted CFB mean A1c and weight for 0.5 mg semaglutide were -1.5 % and -3.4 kg, and at 52 weeks, after switching to 3.0 mg dulaglutide dosed with escalation for 26 weeks, these were -1.7 % and -4.8 kg, respectively. Model-predicted mean A1c and weight CFB for 1.0 mg semaglutide after 26 weeks were -1.8 % and -4.9 kg, and at 52 weeks, after switching to 4.5 mg dulaglutide with dose escalation, these values were -1.8 % and -5.4 kg, respectively. In conclusion, switching from semaglutide 0.5 mg QW to dulaglutide 3.0 mg QW and from 1 mg semaglutide QW to dulaglutide 4.5 mg QW predicted additional and comparable CFB A1c, respectively, but with greater weight loss for both modeled scenarios. Disclosure L. Tham: Employee; Self; Eli Lilly and Company. K. M. Pantalone: Consultant; Self; AstraZeneca, Bayer Inc., Corcept Therapeutics, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Research Support; Self; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk. K. M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Tolerion, Inc., Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Elsevier, Novo Nordisk, Other Relationship; Self; UpToDate, Research Support; Self; Abbott, Sanofi-Aventis, Viacyte, Inc. K. M. Munir: None. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. M. Konig: Employee; Self; Eli Lilly and Company. A. Kwan: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company.