Agent for Type 2 Diabetes Glucagon-Like Peptide-1 (GLP-1) Analogue

摘要

Glucagon-like peptide-1 (GLP-1) has significant effects on insulin secretion and glucose regulation and levels of this gastrointestinal hormone are reduced in type 2 diabetes. However, exogenous GLP-1 is rapidly degraded by enzymatic cleavage and GLP-1 analogues are currently under investigation as treatments for this metabolic disorder. CJC-1131 is covalently bound to serum albumin in vivo and is thereby protected from degradation. Preclinical studies have demonstrated that CJC-1131 displays a spectrum of activity similar to GLP-1, with long-term control of hyperglycemia and inhibition of gastric emptying in rats and dogs, and an extended albumin-adopted pharmacokinetic profile. Safety studies in humans, dogs and rats also demonstrated that this compound is not associated with immunogenic or toxic effects. Clinical investigations have indicated that CJC-1131 significantly reduces glycemia in type 2 diabetic patients and enhances the metformin-induced reduction in glycosylated hemoglobin. A novel diluent for CJC-1131 has resulted in improvement in the tolerability profile of the compound by reducing the incidence of nausea and vomiting.