Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Cui, Qiaoli; Liao, Yijing; Jiang, Yaojing; Huang, Xiaohang; Tao, Weihong; Zhou, Quanquan; Shao, Anna; Zhao, Ying; Li, Jia; Ma, Anran; Wang, Zhihong; Zhang, Li; Yang, Zunyuan; Liang, Yinan; Wu, Minglin; Yang, Zhenyan; Zeng, Wen; Wang, Qinghua
• Is Part Of: Journal of endocrinology. Volume 248:Issue 2(2021)
• Page Start: 145
• Page End: 154
• Publication Date: 2021-02
• Subjects: GLP-1 -- supaglutide -- diabetes -- glucose homeostasis -- obesity; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/JOE-20-0255
• Languages: English
• ISSNs: 0022-0795

Abstract

Abstract : Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t1/2 < 2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and β-cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide's therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-week intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.