Heimann Andrea S, Singh Prachi, Ferro Emer S, Greenway Frank, Krongrad Arnon
Proteimax Biotechnology Israel, Caesarea, Israel.
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Diabetes Metab Res Rev. 2025 Jul;41(5):e70056. doi: 10.1002/dmrr.70056.
Conformational-sensitive antibodies were used to identify the orally active peptide DIIADDEPLT (Pep19) as an inverse agonist of cannabinoid type 1 receptor. Pep19 safely improved metabolic parameters in murine models of diet-induced obesity, and in healthy dogs.
To evaluate Pep19's impact on quality of life and body composition in obese adults, hypothesising that the metabolic effects of Pep19 observed in animal models could translate to humans.
Subjects, males (n = 12) and females (n = 12), from 46 to 59 years old, weighing 91-106 kg, body mass index between 30 and 35 kg/m, were evaluated over 60 days in a placebo-controlled, triple-blinded clinical trial; participants received either a placebo, 2 or 5 mg Pep19 capsules once daily at bedtime. The primary endpoint was a broad measure of quality of life assessed using validated questionnaires. The key secondary endpoints included weight loss, reduction in visceral fat (measured by dual-energy X-ray absorptiometry), and changes in waist, hip, and chest measurements.
Pep19 was well tolerated with no reported adverse effects. Remarkable reductions in visceral fat were observed in the 5 mg Pep19 group, with a 17 ± 4.7% loss (p < 0.05), without any change in lean mass. Additionally, sleep quality improved significantly by 35 ± 10% in the 2 mg Pep19 group and 25 ± 16% in the 5 mg Pep19 group (p < 0.05). In the 5 mg Pep19 group, significant reductions in body weight and waist circumferences were also observed (p < 0.05).
Despite the limitations related to the use of convenience sampling, a small sample size, and a short intervention duration, which may restrict generalisation and health claims, Pep19 demonstrates exceptional innovative potential as a novel approach to reduce visceral fat and improve sleep quality.
构象敏感抗体被用于鉴定口服活性肽DIIADDEPLT（Pep19）为1型大麻素受体的反向激动剂。Pep19可安全改善饮食诱导肥胖小鼠模型及健康犬的代谢参数。
评估Pep19对肥胖成年人生活质量和身体成分的影响，假设在动物模型中观察到的Pep19的代谢效应可转化至人类。
在一项安慰剂对照、三盲临床试验中，对年龄在46至59岁、体重91 - 106 kg、体重指数在30至35 kg/m²之间的男性（n = 12）和女性（n = 12）受试者进行了60天的评估；参与者在睡前每天服用一次安慰剂、2毫克或5毫克Pep19胶囊。主要终点是使用经过验证的问卷对生活质量进行的广泛评估。关键次要终点包括体重减轻、内脏脂肪减少（通过双能X线吸收法测量）以及腰围、臀围和胸围的变化。
Pep19耐受性良好，未报告不良反应。在5毫克Pep19组中观察到内脏脂肪显著减少，减少了17±4.7%（p < 0.05），瘦体重无任何变化。此外，2毫克Pep19组的睡眠质量显著提高了35±10%，5毫克Pep19组提高了25±16%（p < 0.05）。在5毫克Pep19组中，还观察到体重和腰围显著降低（p < 0.05）。
尽管存在与使用便利抽样、样本量小和干预持续时间短相关的局限性，这可能会限制推广和健康声明，但Pep19作为一种减少内脏脂肪和改善睡眠质量的新方法，展现出了非凡的创新潜力。
