Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes.
OBJECTIVE
To evaluate the effect of exenatide on gastric emptying (GE) in type 2 diabetes using scintigraphy.


METHODS
Seventeen subjects with type 2 diabetes participated in a randomized, single-blind, 3-period, crossover study. In each 5-day period, 5 or 10 microg exenatide or placebo was administered subcutaneously BID. Oral antidiabetic treatments were continued. The presence of cardiac autonomic neuropathy was assessed during screening. On day 5, after the morning dose, subjects consumed a 450-kcal breakfast containing (99m)Tc-labeled eggs and (111)In-labeled water, and GE was measured by scintigraphy. Plasma glucose and insulin, perceptions of appetite, and plasma exenatide were also quantified.


RESULTS
Exenatide slowed GE of both solid and liquid meal components [solid (T(50)(90% confidence interval [CI]); placebo, 60(50-70) min; 5 microg exenatide, 111(94-132) min; 10 microg exenatide, 169(143-201) min; both P<0.01); liquid (T(50)(90% CI), placebo, 34(25-46) min; 5 microg exenatide, 87(65-117) min; 10 microg exenatide, 114(85-154) min; both P<0.01)]. GE was not different between subjects with cardiac autonomic neuropathy (n=7), compared with those without (n=10) (P>/=0.68). Exenatide reduced postprandial glucose (area under the curve [AUC((0-6 h))]) by 69-76% and peak insulin (C(max)) by 84-86% compared with placebo. There was an inverse relationship between the postprandial rise in glucose (AUC((0-3 h))) and GE (solid T(50), r=-0.49, P<0.001).


CONCLUSIONS
Exenatide slows GE substantially in type 2 diabetes, which could be an important mechanism contributing to the beneficial effect of exenatide on postprandial glycemia.
Linnebjerg
Helle
H
Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, GU20 6PH, UK. linnebjerg_helle@lilly.com
Park
Soomin
S
Kothare
Prajakti A
PA
Trautmann
Michael E
ME
Mace
Kenneth
K
Fineman
Mark
M
Wilding
Ian
I
Nauck
Michael
M
Horowitz
Michael
M
D000368:Aged; D001066:Appetite / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004361:Drug Tolerance; D000077270:Exenatide; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D019518:Postprandial Period; D012449:Safety; D016037:Single-Blind Method; D014688:Venoms / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide