Potential Therapeutic Levels of Glucagon-Like Peptide I Achieved in Humans by a Buccal Tablet

Abstract

OBJECTIVE Glucagon-like peptide I(7–36) (GLP-I) amide, an endogenous incretin, has been identified as a potential adjunct to the treatment of NIDDM and has been studied following intravenous and subcutaneous injection. A mucoadhesive buccal GLP-I tablet containing 119 nmol has been developed to provide transmucosal absorption as a possible alternative to injection treatment. RESEARCH DESIGN AND METHODS Eight healthy volunteers received a single tablet under fasting conditions in this randomized double-blind placebo-controlled study. A total GLP-I immunoreactivity was measured using COOH-terminal radioimmunoassay (RIA) (total peptide activity) and NH2-terminal RIA (active, nondegraded peptide). RESULTS The mean (± SE) peak GLP-I concentration was 117 ± 19 pmol/l and occurred 30 ± 4 min after application. The mean placebo-adjusted area under curve was 8,145 ± 873 pmol · min−1 · l−1, consistent with a relative bioavailability of 7% versus intravenous injection and 47% versus subcutaneous injection. The levels of active peptide increased in parallel with total GLP-I. Half-life of peptide activity after buccal administration was 27 and 24 min measured with COOH-terminal and NH2-terminal RIA, respectively. Placebo adjusted insulin concentrations increased to a peak of 252 ± 57 pmol/l, glucose decreased 1.4 ± 0.2 mmo/l, and glucagon decreased 17 ± 3 ng/l, consistent with the increase in plasma GLP-I concentrations. CONCLUSIONS Therapeutic plasma levels of GLP-I in humans were achieved after a single buccal tablet. No increased degradation of GLP-I was found in the buccal mucosa compared to subcutaneous tissue. This alternative treatment form may be feasible in in the future for NIDDM.