Pharmacokinetics and tolerability of a novel long acting glucagon‐like‐peptide‐1 analog CJC‐1131

Aims A reactive chain, which electively binds to albumin, was added to a Glucagon‐Like‐Peptide‐1 (GLP‐1) derivative, forming the novel compound CJC‐1131. Binding to albumin is expected to prolong the half‐life of GLP‐1 from minutes to days, and thus to render it a possible treatment for type II diabetes. Methods Single doses of CJC‐1131 or placebo were s.c. administered to healthy subjects and to type II diabetic patients after a 9 days wash‐out of their anti‐diabetic medication. Results CJC‐1131 was quickly absorbed from the subcutaneous space, Cmax showed dose proportionality in the range of 1.5 ‐ 9.5 μg/kg. The half‐life of CJC‐1131 varied from 9.5 ‐ 15.5 days in healthy subjects and from 5.4 ‐ 17.7 days in patients. The MTD in healthy subjects was established at 12μg/kg due to increasing nausea and vomiting probably to a fraction of unbound GLP‐1. Patients receiving doses up to 12 μg/kg CJC‐1131 responded well to pre‐medication with metoclopramide. Average blood glucose levels in patients decreased on day 1 dose proportionally with a maximum decrease of 4.1 mmol/L. Some effect on fasting blood glucose was still present on day 2. Conclusion A major prolongation of the half‐life of GLP‐1 was achieved. Clinical Pharmacology & Therapeutics (2005) 77 , P56–P56; doi: 10.1016/j.clpt.2004.12.102