Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers.
Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol. kg(-1). min(-1)) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 +/- 0.3 vs. saline, 2.2 +/- 0.3 mmol/l, P < 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 +/- 79 vs. saline 1,075 +/- 93 kcal, P = 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.
Edwards
C M
CM
Endocrine Unit, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.
Stanley
S A
SA
Davis
R
R
Brynes
A E
AE
Frost
G S
GS
Seal
L J
LJ
Ghatei
M A
MA
Bloom
S R
SR
D000082:Acetaminophen / Q000097:blood; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D003864:Depression, Chemical; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D000077270:Exenatide; D005215:Fasting / Q000378:metabolism; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D006728:Hormones / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008116:Lizards / Q000502:physiology*; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D011498:Protein Precursors / Q000097:blood; D012528:Satiety Response / Q000187:drug effects; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D014688:Venoms; D000082:Acetaminophen; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide