A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes

Aim To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Japanese participants with type 2 diabetes (T2D). Methods This phase 1, double-blind, placebo-controlled, parallel-dose, multiple-ascending dose study randomized participants to once-weekly subcutaneous tirzepatide or placebo. The tirzepatide treatment groups were: 5 mg (5 mg, weeks 1-8), 10 mg (2.5 mg, weeks 1-2; 5 mg, weeks 3-4; 10 mg, weeks 5-8), and 15 mg (5 mg, weeks 1-2; 10 mg, weeks 3-6; 15 mg, weeks 7-8). The primary outcome was tirzepatide safety and tolerability. Results Forty-eight participants were randomized. The most frequently reported treatment-emergent adverse events (AEs) were decreased appetite and gastrointestinal AEs, which were generally dose-dependent and mild in severity. The plasma tirzepatide concentration half-life was approximately 5 days. After 8 weeks of treatment, fasting plasma glucose decreased from baseline with tirzepatide versus placebo; the least squares (LS) mean decrease compared with placebo (95% confidence interval [CI]) was 52.7 (35.9-69.6), 69.1 (52.3-85.9), and 68.9 (53.2-84.6) mg/dL in the 5-, 10-, and 15-mg treatment groups, respectively (P < .0001 for all treatment groups). Tirzepatide also resulted in LS mean decreases from baseline versus placebo at 8 weeks in HbA1c up to 1.6% (95% CI 1.2%-1.9%; P < .0001 for all treatment groups) and body weight up to 6.6 kg (95% CI 5.3-7.9; P < .0001 for all treatment groups). Conclusions All tirzepatide doses were well tolerated. The safety, tolerability, PK, and PD profiles of tirzepatide support further evaluation of once-weekly dosing in Japanese people with T2D.

Automated summary

The study demonstrated that Tirzepatide is well tolerated in Japanese patients with T2D, showing significant improvements in blood glucose control and weight management.