A novel GIP analogue, ZP 4165, enhances glucagon‐like peptide‐1‐induced body weight loss and improves glycaemic control in rodents

PK Nørregaard, MA Deryabina… - Diabetes, Obesity …, 2018 - Wiley Online Library
PK Nørregaard, MA Deryabina, P Tofteng Shelton, JU Fog, JR Daugaard, PO Eriksson…
Diabetes, Obesity and Metabolism, 2018Wiley Online Library
Aim To investigate the effects of the novel glucose‐dependent insulinotropic polypeptide
(GIP) analogue, ZP 4165, on body weight and glycaemic control in rodents, and to
investigate if ZP 4165 modulates the anti‐obesity and anti‐hyperglycaemic effects of a
glucagon‐like peptide‐1 (GLP‐1) agonist (liraglutide). Methods The acute insulinotropic
effect of ZP 4165 was investigated in rats during an oral glucose tolerance test. The long‐
term effects of ZP 4165 on body weight and glycaemic control, either alone or in combination …
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.
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