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ICA6150349, a Highly Selective Glucagon Agonist, in Combination with Exenatide Significantly Reduces Weight and Glucose in Obese and Diabetic Rats
- Source :
- Diabetes. 67
- Publication Year :
- 2018
- Publisher :
- American Diabetes Association, 2018.
-
Abstract
- ICA6150349, a 38-amino acid analog of glucagon, is peptidase resistant and highly selective for the glucagon receptor. ICA6150349 continuously infused SC at 50 mcg/kg/d (ED50) in DIO LE rats reduced weight (21%), fat mass (37%), and food intake (17%) and normalized triglycerides and cholesterol to lean control levels. ICA6150349 (50 mcg/kg/d) in combination with exenatide (10 mcg/kg/d) further reduced weight (38%), fat mass (70%), and food intake (52%) and also normalized glucose and lipids to lean control levels. ICA6150349 continuously infused at 50 mcg/kg/d in ZDF rats increased HbA1c (1.3%), reduced weight (29%), fat mass (42%), and food intake (13%) and normalized triglycerides (66%) and cholesterol (38%) to lean control levels. ICA6150349 (50 mcg/kg/d) in combination with exenatide (10 mcg/kg/d) decreased HbA1c (1.5%), off-setting the increase seen with ICA6150349 monotherapy. The ICA6150349 and exenatide combination reduced weight (19%), fat mass (25%), food intake (29%) cholesterol (27%) and triglycerides (41%). In rodent models of obesity/T2D, ICA6150349 in combination with exenatide can significantly reduce weight, fat mass, glucose and lipids, sometimes normalizing these parameters to lean control levels. Disclosure M. Paulik: Employee; Self; Intarcia Therapeutics, Inc.. T. Tlusty: None. M.K. Grizzle: None. M. Copeland: None. S. Weng: None. W.C. Blackwell: Employee; Self; Intarcia Therapeutics, Inc. V. Srivastava: Employee; Self; Intarcia Therapeutics, Inc. J. Way: Employee; Self; Intarcia Therapeutics, Inc. S. Roller: Employee; Self; Intarcia Therapeutics, Inc.. D. Zane: None. R. Hodge: Employee; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc. A.A. Young: Employee; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; GlaxoSmithKline plc. P.L. Feldman: Employee; Self; Intarcia Therapeutics, Inc..
- Subjects :
- Agonist
medicine.medical_specialty
medicine.drug_class
business.industry
Cholesterol
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Zdf rats
Highly selective
medicine.disease
Obesity
Glucagon
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
chemistry
Internal medicine
Internal Medicine
medicine
business
Glucagon receptor
Exenatide
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi...........5098fe4d71a1e3811239311092ffbb43