GLP-1 TABLET IN TYPE-2 DIABETES IN FASTING AND POSTPRANDIAL CONDITIONS

OBJECTIVE - To examine the absorption of glucagon-like peptide (GLP)-1 (7-36) amide from the buccal mucosa of type 2 diabetic patients. Previ ously, the effects of the peptide have been studied following intraven ous and subcutaneous injection. Now, a mucoadhesive, biodegradable buc cal GLP-1 tablet (9 mm) containing 119 nmol has been developed as a po ssible alternative to injection. RESEARCH DESIGN AND METHODS-A total o f 10 type 2 diabetic patients received a single tablet under fasting c onditions and before a standard meal in this randomized placebo-contro lled study. RESULTS - The mean peak GLP-1 concentration was 125.1 pmol /l and occurred 30 min after application. The mean placebo-adjusted ar ea under the curve was 5,334 min pmol/l, consistent with a relative bi oavailability of 6% vs, intravenous injection and 42% vs. subcutaneous injection. The hall-life of total peptide activity after buccal admin istration was 17 min. The placebo-adjusted glucose concentrations decr eased by 1.4 mmol/l in fasting experiments and by 4.2 mmol/l after a s tandard mixed meal. In the fasting state at 30 min, plasma insulin inc reased by 185% and glucagon decreased by 20%, consistent with the incr ease in plasma GLP-1 concentrations. The peptide exerted a significant insulinotropic effect during meals (calculated as an insulinogenic in dex, 0-120 min; 84.1 vs. 45.7 in placebo experiments). CONCLUSIONS - P otentially therapeutic plasma levels of GLP-1 were achieved after admi nistration of a single buccal tablet in type 2 diabetic patients. The peptide had a marked glucose-lowering effect during the first 2 h. Thi s new GLP-1 tablet may become a feasible alternative treatment for typ e 2 diabetic patients, although a more prolonged pharmacokinetic profi le is required.