Evaluation of the Anti-Obesity Effect of Sitagliptin in Animal Model of Obesity

  • Mohit Kulmi Assistant Professor, Department of Pharmacology, Government Medical College, Ratlam, M.P.
  • Pooja Reddy Professor & Head, Department of Pharmacology, Sri Aurobindo Medical College & Postgraduate Institute, Indore, M.P.
  • Chhaya Goyal Professor, Department of Pharmacology, Sri Aurobindo Medical College & Postgraduate Institute, Indore, M.P.
Keywords: Anti-Obesity Drugs; Weight Loss Agents; high fat diet; sitagliptin, orlistat.


Background: Obesity is a chronic disorder which involves an excess accumulation of body fat.  It is a growing health problem of increasing prevalence in many countries, reaching alarming proportions not only in adults, but also among children and adolescents which leads to substantial increase in morbidity, and mortality. The use of antiobesity drugs in management of obesity is vital. Many attempts have been made to develop novel drugs to treat obesity and several of these drugs have been withdrawn from the market because of various side effects. GLP-1 agonist and the pathways associated with it are a new potential and promising targets for the treatment of obesity.

Objective: : (1) To evaluate the anti-obesity effect of orlistat (2) To evaluate the anti-obesity effect of sitagliptin (3) To compare the anti-obesity effect of orlistat and sitagliptin in animal model of obesity.

Methods: This study was a prospective study of 17 weeks duration. Obesity due to high fat diet was induced in rats over a period of 17 weeks. Orlistat and sitagliptin were administered for 5 weeks and various parameters like body weight, blood glucose, food intake & BMI were measured over a period of 5 weeks.

Results: In this study upon administration of orlistat there was a gradual loss in weight in rats. Sitagliptin showed significant decline in weight (P<0.05) in rats. It also showed statistically significant (P<0.05) reduction in blood glucose among all the groups. Orlistat and sitagliptin had no significant effect on food intake. Reduction in BMI lead to reduction in Blood glucose levels of rats.

Conclusion: Sitagliptin showed the most reduction of blood glucose, it also showed reduction in total body weight. Orlistat was found to be least efficacious in terms of reduction in total body weight, food intake, blood glucose and BMI in rats.


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1. Wang, Y.C., McPherson, K., Marsh, T., Gortmaker, S.L. & Brown, M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378, 815–825 (2011).
2. Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373: 1083–96.
3. Ahirwar R, Mondal P. Prevalence of obesity in India: A systematic review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019;13(1):318-321.
4. Kopelman PG. Obesity as a medical problem. Nature 2000; 404: 635–43.
5. Poirier P, Giles TD, Bray GA, Hong Y, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Circulation 2006;113:898-918. Pubmed PMID: 16380542
6. Hainer V, Toplak H, Mitrakou A. treatment modalities of obesity: what fits whom? Diabetic Care 2008;31:269-77. Pubmed PMID: 18227496
7. Rössner S, Sjöström L, Noack R et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obesity 2000;8:49–61.
8. Kim, G.W., Lin, J.E., Blomain, E.S. & Waldman, S.A. New advances in modelsand strategies for developing anti-obesity drugs. Expert Opin. Drug Discov.8, 655–671 (2013).
9. Druce M, Small C, Bloom S. Minireview: Gut Peptides Regulating Satiety. Endocrinology. 2004;145(6):2660-2665.
10. Tang-Christensen M, Vrang N, Larsen P. Glucagon-like peptide 1(7-36) amide's central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes. 1998;47(4):530-537.
11. Frank L. Greenway, Eduardo Dunayevich, Gary Tollefson, Janelle Erickson, Maria Guttadauria, Ken Fujioka, Michael A. Cowley. Naltrexone/Bupropion Therapy for Weight Loss J Clin Endocrinol Metab, December 2009, 94(12):4898–4906.
12. Lei F, Zhang X, Wang W, Xing D, Xie W, Su H et al. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J ObesRelatMetabDisord. 2007;31(6):1023-1029.
13. Novelli E, Diniz Y, Galhardi C, Ebaid G, Rodrigues H, Mani F et al. Anthropometrical parameters and markers of obesity in rats. Laboratory Animals. 2007;41(1):111-119.
14. Shafrir E, Ziv E. A useful list of spontaneously arising animal models of obesity and diabetes. AJP: Endocrinology and Metabolism. 2009;296(6):E1450-E1452.
15. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res 2007;125:451-72.
16. Buettner R, Schölmerich J, Bollheimer L. High-fat Diets: Modeling the Metabolic Disorders of Human Obesity in Rodents*. Obesity. 2007;15(4):798-808.
17. Mittendorfer B, Ostlund R, Patterson B, Klein S. Orlistat Inhibits Dietary Cholesterol Absorption. Obesity Research. 2001;9(10):599-604.
18. Shimasaki T, Masaki T, Mitsutomi K, Ueno D, Gotoh K, Chiba S et al. The Dipeptidyl Peptidase-4 Inhibitor Des-Fluoro-Sitagliptin Regulates Brown Adipose Tissue Uncoupling Protein Levels in Mice with Diet-Induced Obesity. PLoS ONE. 2013;8(5):e63626.
19. Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regulatory Peptides. 1999;85(1):9-24.
20. Torgerson J, Hauptman J, Boldrin M, Sjostrom L. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2003;27(1):155-161.
21. Reimer R, Grover G, Koetzner L, Gahler R, Juneja P, Lyon M et al. Sitagliptin Reduces Hyperglycemia and Increases Satiety Hormone Secretion More Effectively When Used with a Novel Polysaccharide in Obese Zucker Rats. Journal of Nutrition. 2012;142(10):1812-1820.
22. Ganz M, Wintfeld N, Li Q, Alas V, Langer J, Hammer M. The association of body mass index with the risk of type 2 diabetes: a case–control study nested in an electronic health records system in the United States. DiabetolMetabSyndr. 2014;6(1):50.
How to Cite
Kulmi M, Reddy P, Goyal C. Evaluation of the Anti-Obesity Effect of Sitagliptin in Animal Model of Obesity. Int Arch BioMed Clin Res [Internet]. 2020Dec.30 [cited 2021Jan.26];6(4):PH11-PH15. Available from: http://iabcr.org/index.php/iabcr/article/view/647