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Liraglutide: short-lived effect on gastric emptying -- long lasting effects on body weight.

AbstractAIM:
Previous studies with the novel once daily glucagon-like peptide-1 (GLP-1) analogue liraglutide and the GLP-1 receptor agonist exenatide have revealed profound insulinotrophic and antidiabetic effects, but also potent effects on gastric emptying (GE) and long-term and lasting reductions in body weight. In this study, we examined the acute and chronic effects of two different GLP-1 analogues with different pharmacokinetic profiles on GE, food intake and body weight.
METHODS:
On the basis of a series of dose-finding studies, the doses of exenatide and liraglutide with similar acute anorectic effects were identified. GE was assessed using a standard acetaminophen release assay. After the acute test, rats were dosed bi-daily for 14 days in which period food intake and body weight was monitored. On day 14, the GE rate was reassessed.
RESULTS:
While both compounds exerted robust acute reductions in GE, the effect was markedly diminished following 14 days of dosing with liraglutide. In contrast, exenatide-treated rats still displayed a profound reduction in GE at the 14-day time-point. Both compounds exerted similar effects on body weight.
CONCLUSION:
The data suggest that the 'gastric inhibitory' GLP-1 receptors in rats are subject to desensitization/tachyphylaxis but that this effect is dependent on full 24-h exposure as obtained by liraglutide. The body weight-lowering effects of GLP-1 receptor stimulation are not subject to desensitization. These data indicate that regulation of appetite signals in the brain, and not GE, is the main mechanism for liraglutide-induced weight loss.
AuthorsJ Jelsing, N Vrang, G Hansen, K Raun, M Tang-Christensen, L Bjerre Knudsen
JournalDiabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 14 Issue 6 Pg. 531-8 (Jun 2012) ISSN: 1463-1326 [Electronic] England
PMID22226053 (Publication Type: Journal Article)
Copyright© 2012 Blackwell Publishing Ltd.
Chemical References
  • Peptides
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide
Topics
  • Animals
  • Appetite Regulation (drug effects)
  • Eating (drug effects)
  • Exenatide
  • Gastric Emptying (drug effects)
  • Glucagon-Like Peptide 1 (analogs & derivatives, pharmacokinetics, pharmacology)
  • Hippocampus (drug effects)
  • Injections, Intravenous
  • Liraglutide
  • Male
  • Obesity (drug therapy)
  • Peptides (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Venoms (pharmacology)
  • Weight Loss (drug effects)

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