1. ICA6150349, a Highly Selective Glucagon Agonist, in Combination with Exenatide Significantly Reduces Weight and Glucose in Obese and Diabetic Rats
- Author
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Mary K. Grizzle, Ved Srivastava, Rebecca J. Hodge, Mark A. Paulik, Andrew A. Young, Paul L. Feldman, Tom Tlusty, Shane Roller, Sharon Weng, Marci Copeland, William Blackwell, James M. Way, and Doris Zane
- 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 - 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..
- Published
- 2018