A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents.

Autor: Nørregaard PK; Zealand Pharma A/S, Glostrup, Denmark., Deryabina MA; Zealand Pharma A/S, Glostrup, Denmark., Tofteng Shelton P; Zealand Pharma A/S, Glostrup, Denmark., Fog JU; Zealand Pharma A/S, Glostrup, Denmark., Daugaard JR; Zealand Pharma A/S, Glostrup, Denmark., Eriksson PO; Zealand Pharma A/S, Glostrup, Denmark., Larsen LF; Zealand Pharma A/S, Glostrup, Denmark., Jessen L; Zealand Pharma A/S, Glostrup, Denmark.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2018 Jan; Vol. 20 (1), pp. 60-68. Date of Electronic Publication: 2017 Jul 27.
DOI: 10.1111/dom.13034
Abstrakt: Aim: To 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).
Methods: The 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.
Results: ZP4165 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.
Conclusions: ZP4165 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.)
Databáze: MEDLINE
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