Zou Yang, Jiang Fan, Sun Chan, Zhao Chunyang, Qian Hongjie, Jia Jingying, Yu Chen, Chen Hong, Wang Mingli, Chen Qian
Drug Clinical Trial Center, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, China.
Diabetes Obes Metab. 2025 Feb;27(2):816-824. doi: 10.1111/dom.16080. Epub 2024 Dec 1.
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).
This phase 1, randomised, double-blind, placebo-controlled study enrolled adult participants with body mass index (BMI) ≥28 kg/m. 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.
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 (t) 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.
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.
本研究旨在评估新型胰高血糖素样肽-1受体激动剂诺利糖肽（SHR20004）在中国非糖尿病肥胖受试者中的安全性、药代动力学和药效学。
本1期随机、双盲、安慰剂对照研究纳入了体重指数（BMI）≥28 kg/m²的成年受试者。研究采用滴定法，每位受试者每日注射诺利糖肽3至6周，直至达到每日0.18、0.24、0.30或0.36 mg的最终剂量。每个剂量组由10名受试者组成，其中8名接受诺利糖肽治疗，2名接受安慰剂治疗。在整个研究过程中进行安全性评估，并评估药代动力学和药效学。
大多数治疗中出现的不良事件为轻度至中度，无严重不良事件或因不良事件导致退出研究。诺利糖肽每日给药4天后血药浓度达到稳态，无明显蓄积。稳态时平均消除半衰期（t）在9.90至11.8小时之间。治疗结束时，安慰剂组和各治疗组与基线相比的平均体重减轻分别为-1.89、-3.26、-5.45、-4.35和-7.46 kg。各诺利糖肽治疗组观察到的体重和BMI降低幅度均大于安慰剂组，且随着给药时间延长呈增加趋势。
中国非糖尿病肥胖受试者对采用滴定法每日给药的诺利糖肽耐受性良好，并显示出潜在的减肥治疗效果。
