Effect of Short Term Sibutramine Supplementation on Appetite Suppression and Related Metabolic Responses


 Sibutramine hydrochloride monohydrate, obesity, appetite, leptin, ghrelin, adiponectin.

How to Cite

Swati Jain, Saroj K. Verma, Vijay K. Singh, & Som Nath Singh. (2012). Effect of Short Term Sibutramine Supplementation on Appetite Suppression and Related Metabolic Responses. Journal of Pharmacy and Nutrition Sciences, 2(2), 165–171. https://doi.org/10.6000/1927-5951.2012.02.02.8


The appetite suppressing property of Sibutramine is well reported. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced in male Sprague Dawley rats by its short term supplementation. The effect of the drug on the regulatory hormones and biochemical variables was studied at an oral dose of 10 mg/kg body weight. There was a decrease in food intake of rats by 35.5% in comparison to their basal food intake as well as untreated controls. There was an increase in plasma levels of adiponectin, serotonin and a decrease in IGF-1 and corticosterone in the treated animals. The circulating levels of ghrelin marginally decreased with a corresponding increase in leptin and CCK in case of treated rats. These may be responsible for the anorectic effect of the drug.



Równicka-Zubik J, Góra A, Su?kowska A. The obesity and way for treatment. Wiad Lek 2011; 64: 226-30.

Roh C, Jung U, Jo SK. Screening of anti-obesity agent from herbal mixtures. Molecules 2012; 17: 3630-38. http://dx.doi.org/10.3390/molecules17043630

Harrold JA, Dovey TM, Blundell JE, Halford JC. CNS regulation of appetite. Neuropharmacology 2012; 63: 3-17. http://dx.doi.org/10.1016/j.neuropharm.2012.01.007

Oltmanns KM, Heldmann M, Daul S, et al. Sibutramine promotes amygdala activity under fasting conditions in obese women. Psychopharmacology (Berl) 2012; 221: 693-700. http://dx.doi.org/10.1007/s00213-011-2615-7

McGovern L, Johnson JN, Paulo R, et al. Clinical review: treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials. J Clin Endocrinol Metab 2008; 12: 4600-605. http://dx.doi.org/10.1210/jc.2006-2409

Kanekar A, Sharma M. Pharmacological approaches for management of child and adolescent obesity. J Clin Med Res 2010; 2: 105-11.

McTigue KM, Harris R, Hemphill B, et al. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2003; 139: 933-49.

Barkeling B, Elfhag K, Rooth P, Rössner S. Short-term effects of sibutramine (Reductil) on appetite and eating behavior and the long-term therapeutic outcome. Int J Obes Relat Metab Disord 2003; 27: 693-700. http://dx.doi.org/10.1038/sj.ijo.0802298

Suliburska J, Bogda?ski P, Szuli?ska M, Pupek-Musialik D. Short-Term Effects of Sibutramine on Mineral Status and Selected Biochemical Parameters in Obese Women. Biol Trace Elem Res 2012; in press. http://dx.doi.org/10.1007/s12011-012-9425-6

Joo NS, Kim SM, Kim KM, Kim CW, Kim BT, Lee DJ. Changes of body weight and inflammatory markers after 12-week intervention trial: results of a double-blind, placebo-control pilot study. Yonsei Med J 2011; 52: 242-48. http://dx.doi.org/10.3349/ymj.2011.52.2.242

Weeke P, Andersson C, Fosbøl EL, et al. The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period. BMC Endocr Disord 2010; 10: 3. http://dx.doi.org/10.1186/1472-6823-10-3

Rotstein A, Inbar O, Vaisman N. The effect of sibutramine intake on resting and exercise physiological responses. Ann Nutr Metab 2008; 52: 17-23. http://dx.doi.org/10.1159/000114290

Fischer K, Colombani PC, Wenk C. Metabolic and cognitive coefficients in the development of hunger sensations after pure macronutrient ingestion in the morning. Appetite 2004; 42: 49-61. http://dx.doi.org/10.1016/S0195-6663(03)00116-8

Luscombe GP, Hopcroft RH, Thomas PC, Buckett WR. The contribution of metabolites to the rapid and potent down-regulation of rat cortical ?-adrenoceptors by the putative antidepressant sibutramine hydrochloride. Neuropharmacology 1989; 28: 129-34. http://dx.doi.org/10.1016/0028-3908(89)90048-8

Casado A, Rodríguez VM, Portillo MP, et al. Sibutramine decreases body weight gain and increases energy expenditure in obese Zucker rats without changes in NPY and orexins. Nutr Neurosci 2003; 6: 103-11. http://dx.doi.org/10.1080/1028415031000094264

LeBlanc M, Thibault L. Effect of sibutramine on macronutrient selection in male and female rats. Physiol Behav 2003; 80: 243-52. http://dx.doi.org/10.1016/j.physbeh.2003.07.010

Montogomery R. Determination of glycogen. Arch Biochem Biophys 1957; 67: 378-86. http://dx.doi.org/10.1016/0003-9861(57)90292-8

Halperin ML, Pande SV. Fatty acyl group transport in mitochondria: carnitine palmitoyltransferase EC and the carnitine-acylcarnitine translocase. Methods Enzymol 1979; 56: 368-78. http://dx.doi.org/10.1016/0076-6879(79)56034-0

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-75.

Mulla MSA, Goyal VK, Jana S, Nirogi R. Safety Evaluation of Sibutramine in Wistar Rats. African J Basic Appl Sci 2010; 2: 128-34.

Levin BE, Dunn-Meynell AA. Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats. Am J Physiol Regul Integr Comp Physiol 2000; 279: R2222-R2228.

Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369: 71-77. http://dx.doi.org/10.1016/S0140-6736(07)60033-6

Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661-71.

Chapelot D, Marmonier C, Thomas F, Hanotin C. Modalities of the food intake-reducing effect of sibutramine in humans. Physiol Behav 2000; 68: 299-308. http://dx.doi.org/10.1016/S0031-9384(99)00176-6

Frassetto SS, Della Santa Rubio A, Lopes JJ, et al. Locomotor and peripheral effects of sibutramine modulated by 5-HT2 receptors. Can J Physiol Pharmacol 2006; 84: 1239-44. http://dx.doi.org/10.1139/y06-082

Fabris R, Granzotto M, Pagano C, et al. Effect of sibutramine on glucose metabolism in genetically obese (fa/fa) Zucker rats. Int J Obes Relat Metab Disord 2000; 24: S124-S126. http://dx.doi.org/10.1038/sj.ijo.0801297

Godoy-Matos A, Carraro L, Vieira A, et al. Treatment of obese adolescents with sibutramine: a randomized, double-blind controlled study. J Clin Endocrinol Metab 2005; 90: 1460-65. http://dx.doi.org/10.1210/jc.2004-0263

Berkowitz RI, Wadden TA, Tershakovec AM, Cronquist JL. Behavior therapy and sibutramine for the treatment of adolescent obesity. JAMA 2003; 289: 1805-12. http://dx.doi.org/10.1001/jama.289.14.1805

Anagnostis P, Selalmatzidou D, Sapranidis M, et al. Comparative effects of sibutramine and orlistat on weight loss, glucose metabolism and leptin levels in non-diabetic obese patients: A prospective study. Indian J Endocrinol Metab 2012; 16: 146-47. http://dx.doi.org/10.4103/2230-8210.91214

Berkowitz RI, Fujioka K, Daniels SR, et al. Effects of sibutramine treatment in obese adolescents: a randomized trial. Ann Intern Med 2006; 145: 81-90.

Smith WJ, Underwood LE, Clemmons DR. Effects of caloric or protein restriction on insulin like growth factor-1 (IGF-1) and IGF binding proteins in children and adults. J Clin Endocrinol Metab 1995; 80: 443-49. http://dx.doi.org/10.1210/jc.80.2.443

Baranowska B, Woli?ska-Witort E, Marty?ska L, et al. Sibutramine therapy in obese women--effects on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations. Neuro Endocrinol Lett 2005; 26: 675-79.

Stroubini T, Perrea D, Perelas A, et al. Effect of sibutramine on regional fat pads and leptin levels in rats fed with three isocaloric diets. Eur Cytokine Netw 2008; 19: 149-55.

Sari R, Eray E, Ozdem S, Akbas H, Coban E. Comparison of the effects of sibutramine versus sibutramine plus metformin in obese women. Clin Exp Med 2010; 10: 179-84. http://dx.doi.org/10.1007/s10238-009-0080-y

Derosa G, Maffioli P, Ferrari I, et al. Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients. J Clin Pharm Ther 2011; 36: 592-601. http://dx.doi.org/10.1111/j.1365-2710.2010.01217.x

Bush EN, Shapiro R, Brune ME, et al. Chronic treatment with either dexfenfluramine or sibutramine in diet-switched diet-induced obese mice. Endocrine 2006; 29: 375-81. http://dx.doi.org/10.1385/ENDO:29:2:375

Zanella MT, Ribeiro Filho FF. Emerging drugs for obesity therapy. Arq Bras Endocrinol Metab 2009; 53: 271-80. http://dx.doi.org/10.1590/S0004-27302009000200019

Halford JC, Wanninayake SC, Blundell JE. Behavioral satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacol Biochem Behav 1998; 61: 159-68. http://dx.doi.org/10.1016/S0091-3057(98)00032-X

Guo H, Liu G, Zhong R, Wang Y, Wang D, Xia M. Cyanidin-3-O-?-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells. Lipids Health Dis 2012; 11: 10. http://dx.doi.org/10.1186/1476-511X-11-10

Kang JA, Lee K, Lee KM, et al. Desipramine Inhibits Histamine H1 Receptor-Induced Ca2+. Signaling in Rat Hypothalamic Cells. PLoS One 2012; 7: e36185. http://dx.doi.org/10.1371/journal.pone.0036185

Kim DM, Yoon SJ, Ahn CW, et al. Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women. Diabetes Res Clin Pract 2004; 66: S139-S144. http://dx.doi.org/10.1016/j.diabres.2003.12.008

Polyzos SA, Kountouras J, Zavos C, Tsiaousi E. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab 2010; 12: 365-383. http://dx.doi.org/10.1111/j.1463-1326.2009.01176.x

Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91-100.

Amin A, Dhillo WS, Murphy KG. The central effects of thyroid hormones on appetite. J Thyroid Res 2011; 2011: 306510.

Grover GJ, Mellström K, Malm J. Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity, hyperlipidemia and diabetes. Curr Vasc Pharmacol 2007; 5: 141-54. http://dx.doi.org/10.2174/157016107780368271

Saleh A, Bisher AB. The Physiological alterations induced by Sibutramine anti-obesity drug on the functions of the thyroid gland and the liver: An experimental study on Wistar rats. Indian J Sci Technol 2010; 3: 1129-33.

Keskin L, Sahin I, Bentli R, Senel S, Taskapan C. The effects of orlistat and sibutramine on serum thyroid hormone levels in obese subjects. Endocrine Abstracts, European Congress of Endocrinology; 2006: Glasgow, UK: British Endocrine Societies 2006; 11: P853.

Maes M, Meltzer HY, D'Hondt P, Cosyns P, Blockx P. Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal axis function in depression. Psychoneuroendocrinology 1995; 20: 149-67. http://dx.doi.org/10.1016/0306-4530(94)00049-G

Dronjak S, Spasojevic N, Gavrilovic L, Varagic V. Effects of noradrenaline and serotonin reuptake inhibitors on pituitary-adrenocortical and sympatho-adrenomedullar system of adult rats. Neuro Endocrinol Lett 2007; 28: 614-20.

Fernstrom JD, Fernstrom MH. Monoamines and protein intake: are control mechanisms designed to monitor a threshold intake or a set point? Nutr Rev 2001; 59: S60-5, S66-8.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Copyright (c) 2012 Swati Jain, Saroj K. Verma, Vijay K. Singh , Som Nath Singh