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. Previously, the effects of the peptide have been studied following intravenous and subcutaneous injection. Now, a mucoadhesive, biodegradable buccal GLP-1 tablet (9 mm) containing 119 nmol has been developed as a possible alternative to injection.


METHODS
A total of 10 type 2 diabetic patients received a single tablet under fasting conditions and before a standard meal in this randomized placebo-controlled study.


RESULTS
The mean peak GLP-1 concentration was 125.1 pmol/l and occurred 30 min after application. The mean placebo-adjusted area under the curve was 5,334 min pmol/l, consistent with a relative bioavailability of 6% vs. intravenous injection and 42% vs. subcutaneous injection. The half-life of total peptide activity after buccal administration was 17 min. The placebo-adjusted glucose concentrations decreased by 1.4 mmol/l in fasting experiments and by 4.2 mmol/l after a standard mixed meal. In the fasting state at 30 min, plasma insulin increased by 185% and glucagon decreased by 20%, consistent with the increase in plasma GLP-1 concentrations. The peptide exerted a significant insulinotropic effect during meals (calculated as an insulinogenic index, 0-120 min; 84.1 vs. 45.7 in placebo experiments).


CONCLUSIONS
Potentially therapeutic plasma levels of GLP-1 were achieved after administration of a single buccal tablet in type 2 diabetic patients. The peptide had a marked glucose-lowering effect during the first 2 h. This new GLP-1 tablet may become a feasible alternative treatment for type 2 diabetic patients, although a more prolonged pharmacokinetic profile is required.
Gutniak
M K
MK
Vällingby Medical Center, Stockholm, Sweden. mark.gutniak@mailbox.swipnet.se
Larsson
H
H
Sanders
S W
SW
Juneskans
O
O
Holst
J J
JJ
Ahrén
B
B
D000042:Absorption; D000278:Administration, Buccal; D000368:Aged; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000187:drug effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D013607:Tablets; D052216:Glucagon-Like Peptide 1; D005934:Glucagon