Safety, pharmacokinetics and pharmacodynamics of multiple-dose noiiglutide (SHR20004), a novel GLP-1 receptor agonist, in Chinese obese subjects without diabetes mellitus

Diabetes Obes Metab. 2024 Dec 1. doi: 10.1111/dom.16080. Online ahead of print.

Abstract

Aims: This study aimed to assess the safety, pharmacokinetics and pharmacodynamics of noiiglutide (SHR20004), a novel glucagon-like peptide-1 receptor agonist, in Chinese obese participants without diabetes mellitus (DM).

Materials and methods: This phase 1, randomised, double-blind, placebo-controlled study enrolled adult participants with body mass index (BMI) ≥28 kg/m2. The study used a titration method, each subject received daily noiiglutide injection for 3-6 weeks, until reaching the final dose of 0.18, 0.24, 0.30 or 0.36 mg per day. Each dose group consisted of 10 participants, with eight receiving noiiglutide and two receiving placebos. Safety assessments were conducted throughout the study, and pharmacokinetics and pharmacodynamics were evaluated.

Results: Most treatment-emergent adverse events were of mild to moderate in severity, with no serious adverse event or adverse event led to withdraw. Blood concentration of noiiglutide reached a steady state after daily administration for 4 days, with no significant accumulation. Mean elimination half-life (t1/2) was between 9.90 and 11.8 h at steady state. At the end of treatment, the mean weight loss compared to baseline for the placebo group and each treatment group was -1.89, -3.26, -5.45, -4.35 and -7.46 kg respectively. The weight and BMI reductions observed in each noiiglutide treatment group were greater than those in the placebo group and exhibited an increasing trend with extended administration duration.

Conclusions: Daily administration of noiiglutide using a titration method was well tolerated by Chinese obese participants without DM and showed potential therapeutic effect for weight loss.

Keywords: GLP‐1 analogue; antiobesity drug; clinical trial; obesity therapy; phase I–II study.