A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes

Abstract

Introduction: We aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of orforglipron in Japanese participants with type 2 diabetes.

Materials and methods: This was a double-blind, placebo-controlled, randomized, phase 1 study. In Part A, participants received single doses of orforglipron (2 or 3 mg) or placebo. In Part B, participants received multiple ascending doses of daily oral orforglipron (final target doses: 12, 24, and 45 mg) or placebo for 12 weeks.

Results: Parts A and B enrolled 23 and 60 participants, respectively. The most common treatment-emergent adverse events were gastrointestinal events of mild severity. No severe or serious adverse events were reported. At week 12, median t_max was 5.92-8.00 h, and mean terminal half-life was 51.8-76.1 h. Following multiple ascending doses, orforglipron groups had greater mean reductions from baseline to week 12 in glycemic parameters (fasting glucose: orforglipron 12 mg -64.8 mg/dL, 24 mg -61.1 mg/dL, 45 mg -65.6 mg/dL, placebo 7.4 mg/dL; glycated hemoglobin: orforglipron 12 mg -2.16%, 24 mg -2.17%, 45 mg -2.28%, placebo 0.67%) and body weight (orforglipron 12 mg -2.9 kg, 24 mg -6.3 kg, 45 mg -4.8 kg, placebo 0.3 kg) compared with placebo.

Discussion: In Japanese participants, safety, pharmacokinetic, and pharmacodynamic results were similar to those of previous orforglipron studies. The safety and tolerability of orforglipron were also consistent with those of other glucagon-like peptide-1 receptor agonists. Orforglipron is a potential new treatment option for Japanese patients with type 2 diabetes.

Keywords: Body Weight Loss; Orforglipron; Type 2 diabetes mellitus.