DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.,Journal of Endocrinological Investigation

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DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.
Journal of Endocrinological Investigation ( IF 5.4 ) Pub Date : 2019-11-30 , DOI: 10.1007/s40618-019-01153-z
W Wang _{1,

2} , X Wen ₂ , W Duan ₂ , X Wang ₂ , Y Chen ₂ , J Dong ₂ , Z Yang ₂ , J Fang ₂ , Z Zhou ₂ , G Yao ₂ , Y Fang ₂ , Y Huang ₂

Affiliation

PURPOSE Both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) belong to the incretin family. This study aimed to investigate the pharmacokinetics and pharmacodynamics of DR10601, a fully recombinant hybrid peptide with dual GLP-1/GCG receptor agonistic activity. METHODS The agonistic ability of DR10601 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary cells transfected with GLP-1R or GCGR in vitro. Following s.c. administration, the plasma pharmacokinetics of DR10601 were analysed in male Sprague-Dawley rats. The antiobesity effects and improved glycaemic control of DR10601 in vivo were evaluated by administering DR10601 to high-fat DIO mice and ICR mice as a single dose or repeated s.c. doses once every 4 days for 24 days. RESULTS DR10601 exhibits dual agonistic activity on GLP-1 and glucagon receptors. The plasma half-life of DR10601 in Sprague-Dawley rats following s.c. administration was 51.9 ± 12.2 h. In an IPGTT, a single s.c. dose of DR10601 (30 nmol/kg) produced similar glycaemic control effects and a longer duration of action compared to dulaglutide (10 nmol/kg). Compared with that achieved with liraglutide (40 nmol/kg) s.c. administered daily, DR10601 administered s.c. once every 4 days at 90 nmol/kg exerted a nearly equivalent effect on food intake and significantly reduced the body weights of high-fat DIO mice at 24 days. CONCLUSIONS Repeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.

更新日期：2020-04-21

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