Abstract
Concerns over the development of conditions such as primary pulmonary hypertension and valvular heart disease in patients taking serotonin releasing agents such as dexfenfluramine and fenfluramine led to searches for the agents that worked via serotonin but did not produce the same cardiovascular side effects. Sibutramine is a serotonin and noradrenaline reuptake inhibitor, pharmacologically distinct from these other drugs which are considered serotonin releasing agents, which was originally developed as an antidepressant [1]. Early clinical studies showed sibutramine to be largely devoid of antidepressant properties, but resulted in weight loss [2]. This therefore led to the development of sibutramine as an anti-obesity agent. Sibutramine has now been shown to be effective at producing weight loss in simple obesity and obesity associated with a range of co-morbidities including hypertension, dyslipidaemia and type 2 diabetes, and this chapter will describe its preclinical and clinical pharmacology, efficacy in clinical trials and describe the progress of long-term outcome trials with sibutramine, such as the Sibutramine Cardiovascular OUtcomes Trial (SCOUT study).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Buckett WR, Thomas PC, Luscombe GP (1988) The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation. Prog Neuropsychopharmacol Biol Psychiatry 12(5): 575–584
Weintraub M, Rubio A, Golik A, Byrne L, Scheinbaum ML (1991) Sibutramine in weight control: a dose-ranging, efficacy study. Clin Pharmacol Ther 50(3): 330–337
Luscombe GP, Slater NA, Lyons MB, Wynne RD, Scheinbaum ML, Buckett WR(1990) Effect on radiolabeled-monoamine uptake in vitro of plasma taken from healthy-volunteers administered the antidepressant sibutramine hcl. Psychopharmacology 100: 345–349
Luscombe GP, Hopcroft RH, Thomas PC, Buckett WR (1989) The contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride. Neuropharmacology 28(2): 129–134
Hind ID, Mangham JE, Ghani SP, Haddock RE, Garratt CJ, Jones RW (1999) Sibutramine pharmacokinetics in young and elderly healthy subjects. Eur J Clin Pharmacol 54: 847–849
Jackson HC, Needham AM, Hutchins LJ, Mazurkiewicz SE, Heal DJ (1997) Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat. Brit J Pharmacol 121: 1758–1762
Jackson HC, Hutchins LJ, Mazurkiewicz SE, Heal DJ, Buckett WR (1996) Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat. Brit J Pharmacol 117: 323
Halford JCG, Heal DJ, Blundell JE (1995) Effects in the rat of sibutramine on food-intake and the behavioral satiety sequence. Brit J Pharmacol 114: p387
Brown M, Bing C, King P, Pickavance L, Heal D, Wilding J (2001) Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wister rats independently of hypothalamic neuropeptide Y. Brit J Pharmacol 132(8): 1898–1904
Rolls BJ, Shide DJ, Thorwart ML, Ulbrecht JS (1998) Sibutramine reduces food intake in nondieting women with obesity. Obesity Res 6: 1–11
Hansen DL, Toubro S, Stock MJ, Macdonald IA, Astrup A (1999) The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction [Full text available]. Int J Obesity 23: 1016–1024
Barkeling B, Elfhag K, Rooth P, Rossner S (2003) Short-term effects of sibutramine (Reductil (TM)) on appetite and eating behaviour and the long-term therapeutic outcome. Int J Obesity 27(6): 693–700
Rowley HL, Butler S, Prow MR, Dykes SG, Aspley S, Kilpatrick IC, Heal DJ (2000) Comparison of the effects of sibutramine and other weightmodifying drugs on extracellular dopamine in the nucleus accumbens of freely moving rats. Synapse 38(2): 167–176
Cole JO, Levin A, Beake B, Kaiser PE, Scheinbaum ML (1998) Sibutramine: A new weight loss agent without evidence of the abuse potential associated with amphetamines. J Clin Psychopharmacol 18: 231–236
Connoley IP, Liu YL, Frost I, Reckless IP, Heal DJ, Stock MJ (1999) Thermogenic effects of sibutramine and its metabolites. Brit J Pharmacol 126: 1487–1495
Connoley IP, Frost I, Heal DJ, Stock MJ (1996) Role of beta-adrenoceptors in mediating the thermogenic effects of sibutramine. Brit J Pharmacol 117: p170
King DJ, Devaney N (1988) Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers. Br J Clin Pharmacol 26(5): 607–611
Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC, Biaggioni I, Sharma AM, Jordan J (2002) Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation 106(19): 2459–2465
James WPT (2005) The SCOUT study: risk-benefit profile of sibutramine in overweight high-risk cardiovascular patients. Eur Heart J Supplements 7(L): L44–L48
Finer N, Caterson I, Coutinho W, Van Gaal L, Maggioni A, Sharma A, Torp-Pedersen C, James WPT (2007) Clinically relevant weight loss achieved in high-risk patients during 6-week sibutramine treatment — an analysis from the sibutramine cardiovascular outcomes (SCOUT) trial. Int J Obesity 31: S29
Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K (1996) Double-blind randomized placebo-controlled trial of sibutramine. Obesity Res 4: 263–270
Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, Hesson LA, Osei SY, Kaplan R, Stunkard AJ (2005) Randomized trial of lifestyle modification and pharmacotherapy for obesity. New Eng J Med 353(20): 2111–2120
Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K (1996) Double-blind randomized placebo-controlled trial of sibutramine. Obesity Res 4: 263–270
Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E (1999) Long-term maintenance of weight loss after a very-low-calorie diet: A randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med 106: 179–184
James WPT, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, Saris WHM, Van Gaal LF (2000) Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet 356(9248): 2119–2125
Rissanen A, Taskinen MR (2000) Weight loss on sibutramine treatment for 12 months improves lipid profile in obese type 2 diabetic patients. Diabetologia 43: 657
McNulty SJ, Ur E, Williams G (2003) A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with mefformin. Diabetes Care 26(1): 125–131
Fujioka K, Seaton TB, Rowe E, Jelinek CA, Raskin P, Lebovitz HE, Weinstein SP (2000) Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obesity and Metabolism 2(3): 175–187
Serrano-Rios M, Meichionda N, Moreno-Carretero E (2002) Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Diabetic Med 19(2): 119–124
Norris SL, Zhang XP, Avenell A, Gregg E, Schmid CH, Kim C, Lau J (2004) Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus — A meta-analysis. Arch Intern Med 164(13): 1395–1404
Jordan J, Scholze J, Matiba B, Wirth A, Hauner H, Sharma AM (2005) Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obesity 29(5): 509–516
Berkowitz RI, Wadden RA, Tershakovec AM, Cronquist JL (2003) Behavior therapy and sibutramine for the treatment of adolescent obesity — A randomized controlled trial. JAMA 289(14): 1805–1812
Berkowitz RI, Fujioka K, Daniels SR, Hoppin AG, Owen S, Perry AC, Sothern MS, Renz CL, Pirner MA, Walch JK et al. (2006) Effects of sibutramine treatment in obese adolescents — A randomized trial. Ann Intern Med 145(2): 81–90
Godoy-Matos A, Carraro L, Vieira A, Oliveira J, Guedes EP, Mattos L, Rangel C, Moreira RO, Coutinho W, Appolinario JC (2005) Treatment of obese adolescents with sibutramine: A randomized, double-blind, controlled study. J Clin Endocrinol Metabolism 90(3): 1460–1465
Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A, Sharma A, Brisco W, Deaton R, Shepherd G et al. (2007) Cardiovascular responses to weight management and sibutramine in high risk subjects: an analysis from the SCOUT trial. Eur Heart J doi:10.1093/eurheartj/ehm217
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Birkhäuser Verlag/Switzerland
About this chapter
Cite this chapter
Wilding, J.P.H. (2008). Sibutramine. In: Wilding, J.P.H. (eds) Pharmacotherapy of Obesity. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7425-9_5
Download citation
DOI: https://doi.org/10.1007/978-3-7643-7425-9_5
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-7643-7138-8
Online ISBN: 978-3-7643-7425-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)