Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys

in Journal of Endocrinology
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  • 1 Q Cui, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 2 Y Liao, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 3 Y Jiang, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 4 X Huang, -, Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China
  • 5 W Tao, -, Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China
  • 6 Q Zhou, -, Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China
  • 7 A Shao, -, Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China
  • 8 Y Zhao, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 9 J Li, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 10 A Ma, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 11 Z Wang, Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 12 L Zhang, Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China
  • 13 Z Yang, Primed Non-Human Primate Research Centre, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, China
  • 14 Y Liang, Primed Non-Human Primate Research Centre, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, China
  • 15 M Wu, Primed Non-Human Primate Research Centre, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, China
  • 16 Z Yang, Primed Non-Human Primate Research Centre, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, China
  • 17 W Zeng, Primed Non-Human Primate Research Centre, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, China
  • 18 Q Wang, Division of Endocrinology and Metabolism, Huashan Hospital Fudan University, Shanghai, China

Correspondence: Qinghua Wang, Email: Qinghua.Wang@unityhealth.to

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 beta 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-weeks 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.