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

Diabetes, Obesity and Metabolism - Tập 20 Số 1 - Trang 60-68 - 2018
Pia K. Nørregaard1, Maria A. Deryabina1, Pernille Tofteng Shelton1, Jacob U. Fog1, Jens R. Daugaard1, Per‐Olof Eriksson1, L. F. Larsen1, Lene Jessen1
1Zealand Pharma A/S, Glostrup, Denmark

Tóm tắt

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.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.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.

Từ khóa


Tài liệu tham khảo

The World Health Organization. Global report on diabetes 2016.http://www.who.int/diabetes/global‐report/en/. Accessed April 3 2017.

10.1172/JCI116186

10.1210/jc.2003-030738

10.1038/nm727

10.1007/s00125-009-1422-8

10.1371/journal.pone.0040156

10.2337/diabetes.51.3.652

10.1016/S0006-291X(03)01361-5

10.1021/jm0509997

10.1371/journal.pone.0009590

Martin CM, 1830, A novel acylated form of (d‐Ala(2))GIP with improved antidiabetic potential, lacking effect on body fat stores, Biochim Biophys Acta, 2013, 3407

10.1111/dom.12181

10.1016/j.regpep.2008.11.007

10.1126/scitranslmed.3007218

10.1074/jbc.M113.512046

10.1038/nm.3761

10.1007/s00125-008-1195-5

10.1210/jc.2008-1731

10.1111/dom.12395

10.1042/CS20110006

10.1210/jc.85.10.3575

U.S. Food and Drug Administration. Novo Nordisk briefing document on liraglutide (injection) NDA 22‐341 (Liraglutide (injection) for the treatment of patients with type 2 diabetes) Published in 2009 for the Endocrine and Metabolic Drug Advisory Committee 2 April 2009.https://www.fda.gov. Accessed May 5 2017.

10.1016/j.molmed.2016.03.005

10.1111/bph.13323

10.1210/jc.76.4.912

10.2337/db10-1332

Thông tin
Thông tin xuất bản

Diabetes, Obesity and Metabolism

Tập 20 Số 1

60-68

Thông tin tác giả