Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not

Diabetes. 2007 Jan;56(1):8-15. doi: 10.2337/db06-0565.

Abstract

Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Animals
  • Body Composition / drug effects
  • Body Weight / drug effects*
  • Candy*
  • Energy Intake / drug effects*
  • Energy Metabolism / drug effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacology
  • Hypoglycemic Agents / pharmacology*
  • Liraglutide
  • Nitriles
  • Obesity
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pyrrolidines
  • Rats
  • Rats, Sprague-Dawley
  • Vildagliptin

Substances

  • Hypoglycemic Agents
  • Nitriles
  • Pyrrolidines
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Vildagliptin
  • Adamantane