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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

¹ Department of Pharmacology Research 3, Novo Nordisk A/S, Maaloev, Denmark
² Department of Pharmacology Research 4, Novo Nordisk A/S, Maaloev, Denmark

Address correspondence and reprint requests to K. Raun, Diabetes Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. E-mail: kira{at}novonordisk.com

Abbreviations: AUC, area under the curve; DEXA, dual-energy X-ray absorptiometry; DIO, diet-induced obesity; DPP-IV, dipeptidyl peptidase-IV; GLP-1, glucagon-like peptide-1; OGTT, oral glucose tolerance test

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 ß-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 ß-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of ß-cell to body mass was low.

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