Review article
Obesity and pharmacologic therapy

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Sibutramine

Originally developed as an antidepressant, sibutramine (Meridia) is a β-phenethylamine that inhibits norepinephrine and serotonin reuptake without the release of monoamines [5]. Instead of improving mood, however, treatment led to weight loss. Since 1997, sibutramine has been approved for long-term treatment of obesity. NIH guidelines recommend starting treatment at an oral dose of 10 mg/day [4]. Subsequently, the dose can be increased or decreased by 5 mg/day depending on efficacy and

Leptin

With its discovery in 1994, leptin established adipose as an endocrine organ. Leptin is a hormone released from adipocytes that conveys a message of energy availability to the hypothalamus. Leptin deficiency leads to severe obesity [51]. Leptin acts by means of its receptor to activate a Janus kinase/signal transduction and translation (JAK/STAT) system, which ultimately leads to the decreased expression of neuropeptide Y (NPY), a potent appetite stimulant, and the increased expression of

Summary

Obesity is a chronic, complex, multifactorial disorder with increasing prevalence in modern society. Lifestyle modification has had limited success in treating this disorder. Currently approved pharmacologic treatments for obesity include sibutramine and orlistat, which have been associated with significantly greater weight loss than that seen with dieting alone. In addition, a greater percentage of patients who receive medical treatment achieve weight losses of more than 5% to 10% of their

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References (85)

  • K.M Flegal et al.

    Prevalence and trends in obesity among US adults, 1999–2000

    JAMA

    (2002)
  • J.E Manson et al.

    Obesity in the United States: a fresh look at its high toll

    JAMA

    (2003)
  • M Rosenbaum et al.

    Obesity

    N Engl J Med

    (1997)
  • National Institutes of Health

    National Heart Lung and Blood Institute, and North American Association for the Study of Obesity. The practical guide: identification, evaluation, and treatment of overweight and obesity in adults

    (2000)
  • G.A Bray et al.

    Current and potential drugs for treatment of obesity

    Endocr Rev

    (1999)
  • Centers for Disease Control and Prevention

    Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services interim public health recommendations, November 1997

    JAMA

    (1997)
  • C.K Haddock et al.

    Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials

    Int J Obes Relat Metab Disord

    (2002)
  • D.J Goldstein

    Beneficial health effects of modest weight loss

    Int J Obes Relat Metab Disord

    (1992)
  • D.B Allison et al.

    Annual deaths attributable to obesity in the United States

    JAMA

    (1999)
  • T.A Wadden et al.

    Benefits of lifestyle modification in the pharmacologic treatment of obesity: a randomized trial

    Arch Intern Med

    (2001)
  • G Bakris et al.

    Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension

    J Hypertens

    (2002)
  • S.Z Yanovski et al.

    Obesity

    N Engl J Med

    (2002)
  • D.L Hansen et al.

    The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction

    Int J Obes Relat Metab Disord

    (1999)
  • K.M Walsh et al.

    The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

    Int J Obes Relat Metab Disord

    (1999)
  • A Wirth et al.

    Long-term weight loss with sibutramine: a randomized controlled trial

    JAMA

    (2001)
  • G Fanghanel et al.

    Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension

    Adv Ther

    (2003)
  • F.G McMahon et al.

    Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial

    Arch Intern Med

    (2000)
  • G.A Bray et al.

    Sibutramine produces dose-related weight loss

    Obes Res

    (1999)
  • C Hanotin et al.

    Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study

    Int J Obes Relat Metab Disord

    (1998)
  • G Fanghanel et al.

    Second phase of a double-blind study clinical trial on sibutramine for the treatment of patients suffering essential obesity: 6 months after treatment cross-over

    Int J Obes Relat Metab Disord

    (2001)
  • N Finer et al.

    Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study

    Diabetes Obes Metab

    (2000)
  • K Fujioka et al.

    Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus

    Diabetes Obes Metab

    (2000)
  • G Fanghanel et al.

    A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity

    Int J Obes Relat Metab Disord

    (2000)
  • S.J McNulty et al.

    A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin

    Diabetes Care

    (2003)
  • D.S Bach et al.

    Absence of cardiac valve dysfunction in obese patients treated with sibutramine

    Obes Res

    (1999)
  • Committee for Proprietary Medicinal Products

    Committee for Proprietary Medicinal Products opinion following an article 31 referral: sibutramine

    (2002)
  • F.G McMahon et al.

    Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors

    J Hum Hypertens

    (2002)
  • J.J Sramek et al.

    Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

    J Hum Hypertens

    (2002)
  • L.F Van Gaal et al.

    Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging Study Group

    Eur J Clin Pharmacol

    (1998)
  • L Karhunen et al.

    Effect of orlistat treatment on body composition and resting energy expenditure during a two-year weight-reduction programme in obese Finns

    Int J Obes Relat Metab Disord

    (2000)
  • Hirsch B, editor. New lipase inhibitor completes phase 1 trial. Obes Meds Res News [serial online], 2000:4(8)....
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    Louis J. Aronne has received grants and research support from, or functioned as a consultant or speaker for, the following companies: Roche Pharmaceuticals, Abbott Laboratories, Ortho-McNeil Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi-Synthelabo, TAP Pharmaceuticals, Bristol-Myers Squibb.

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