• Pia K Nørregaard, Maria A Deryabina, Pernille Tofteng Shelton, Jacob U Fog, Jens R Daugaard, Per-Olof Eriksson, Lone F Larsen, and Lene Jessen.
• Zealand Pharma A/S, Glostrup, Denmark.
• Diabetes Obes Metab. 2018 Jan 1; 20 (1): 60-68.

AimTo investigate the effects of the novel glucose-dependent insulinotropic polypeptide (GIP) analogue, ZP4165, on body weight and glycaemic control in rodents, and to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycaemic effects of a glucagon-like peptide-1 (GLP-1) agonist (liraglutide).MethodsThe acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. The long-term effects of ZP4165 on body weight and glycaemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice.ResultsZP4165 showed insulinotropic action in rats. The GIP analogue did not alter the body weight of obese mice but enhanced GLP-1-induced weight loss. In diabetic mice, 4 weeks' dosing with ZP4165 reduced glycated haemoglobin levels vs vehicle by an extent similar to the GLP-1 agonist.ConclusionsZP4165 potentiated the anti-obesity effect of a GLP-1 agonist in obese mice and improved glycaemic control in diabetic mice. These studies support further investigation of dual-incretin therapy as a more effective treatment option than mono GLP-1 medication for type 2 diabetes mellitus and obesity.© 2017 John Wiley & Sons Ltd.

64 keywords...

hide…