Tirzepatide (TZP), a novel dual GIP and GLP-1 receptor agonist (RA), has shown superior glycemic control and weight loss compared to a selective GLP-1 RA. A Phase 1, double-blind, placebo-controlled, randomized, parallel-dose group, 8-week multiple ascending dose study investigated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TZP administered QW in 48 Japanese patients with T2DM. This study consisted of 1 fixed dose (5 mg) and 2 dose titration (2.5-2.5-5-5-10-10-10-10 mg and 5 5 10 10 10 10 15 15 mg) cohorts of TZP. With TZP, there were marked reductions from baseline to Week 8 in fasting serum glucose, HbA1c, and body weight. The half-life of plasma TZP concentration was approximately 5 days and supports QW dosing regimen. All doses of TZP were well tolerated. The most frequently reported treatment-emergent adverse events (AEs) were decreased appetite and gastrointestinal AEs (constipation, diarrhea, abdominal discomfort, abdominal distension, vomiting, and nausea). These AEs were generally dose dependent and mild in severity. The safety, tolerability, PK, and PD profiles of TZP in this study appeared comparable to other Phase 1 and 2 studies in non-Japanese patients with T2DM. The data support Phase 3 development of TZP for QW dosing in Japanese patients with T2DM.

K. Ohwaki: Employee; Self; Eli Lilly and Company. K. Furihata: None. H. Mimura: Employee; Self; Eli Lilly and Company. T. Oura: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T. Imaoka: Employee; Self; Eli Lilly and Company.

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