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

Diabetes Obes Metab. 2012 Jun;14(6):531-8. doi: 10.1111/j.1463-1326.2012.01557.x. Epub 2012 Feb 8.


Aim: 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.

MeSH terms

  • Animals
  • Appetite Regulation / drug effects*
  • Eating / drug effects
  • Exenatide
  • Gastric Emptying / drug effects*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacokinetics
  • Glucagon-Like Peptide 1 / pharmacology
  • Hippocampus / drug effects*
  • Injections, Intravenous
  • Liraglutide
  • Male
  • Obesity / drug therapy*
  • Peptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Venoms / pharmacology
  • Weight Loss / drug effects*


  • Peptides
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide