• anti-obesity drugs;
  • orlistat;
  • rimonabant;
  • sibutramine


  1. Top of page
  2. Abstract
  3. Introduction
  4. Pharmacological treatment for obesity
  5. Conclusion
  6. Competing interests

Obesity is associated with increased risk of conditions such as hypertension, dyslipidaemia, diabetes mellitus, and obstructive sleep apnoea. Pharmacotherapy for obesity should be considered in combination with lifestyle changes in obese patients, or overweight patients with other conditions that put them at risk of developing heart disease. Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use. Sibutramine is a serotonergic and adrenergic drug that reduces food intake. Orlistat is a gastrointestinal lipase inhibitor that interferes with fat absorption. However, it commonly causes flatulence and diarrhoea. Rimonabant is the first of a series of endocannabinoid receptor antagonists. It was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMEA) as an adjunct to diet and exercise in treating obesity in 2006. However, despite the extensive clinical trial data, EMEA announced in 2008 that it has recommended suspension of rimonabant because of its psychiatric side effects. Studies evaluating the long-term safety and efficacy of anti-obesity agents are needed.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Pharmacological treatment for obesity
  5. Conclusion
  6. Competing interests

Obesity, a chronic condition characterized by excess body fat, has become the most common nutritional disorder in developed countries [1]. Its prevalence is increasing rapidly world wide [2]. A previous study estimated that two-thirds of all adults in the United States were obese or overweight, and 4.8% were extremely obese in 2003–2004 [3]. Overweight and obesity are associated with increased risk of conditions such as hypertension, dyslipidaemia, type 2 diabetes, cardiovascular diseases and obstructive sleep apnoea [4–6]. Patients with abdominal obesity might be at greater risk of developing type 2 diabetes and cardiovascular diseases [6, 7].

The body mass index (BMI) is the most commonly used measure of obesity. The BMI is calculated from a person's height and weight (BMI = kg m−2). For adults, overweight is currently defined as a BMI between 25 and 29.9 kg m−2, obesity as a BMI equal to or greater than 30 kg m−2, and extreme obesity as a BMI of 40 kg m−2 or greater [8]. However, BMI is not a good measure of obesity since the body composition of different people with the same BMI can be highly variable. It is not reliable particularly in older and younger people [9]. In addition, it does not reflect intra-abdominal (visceral) fat that is related to the metabolic syndrome and cardiovascular risks [9].

Due to the increase in obesity and the enormous economic burden generated by obesity, its treatment has become one of the most urgent issues in medicine today. If obesity is accepted as a chronic disease, it should be dealt with in the same way as other chronic diseases such as diabetes and hypertension. The treatment of obesity should not be a short-term ‘fix’, but an ongoing life-long process of maintaining normal body weight. The American College of Physicians (ACP) recommends that strategies for managing overweight and obesity should always include lifestyle and behavioural modifications, such as appropriate diet and exercise [10–13]. In addition, the ACP suggests that pharmacological therapy is recommended for people with a BMI ≥30 kg m−2 or those with a BMI >27 kg m−2 and associated co-morbidities such as type 2 diabetes, cardiovascular diseases and obstructive sleep apnoea [10]. Medications should not be used purely for cosmetic reasons [10]. A clinical study has found that the combination of medication and life style management, which includes diet, exercise, and behavioural therapy, has greater effects on weight loss than either medication or lifestyle alone [14]. Therefore, the importance of life style management cannot be over-emphasized.

Pharmacological treatment for obesity

  1. Top of page
  2. Abstract
  3. Introduction
  4. Pharmacological treatment for obesity
  5. Conclusion
  6. Competing interests

The pharmacological treatment for obesity has attracted much attention from both clinicians and patients, although the amount of extra weight loss attributable to it is modest (<5 kg at 1 year) [10]. Nevertheless, this amount of weight loss has been shown to improve insulin sensitivity, glycaemic control, dyslipidaemia and hypertension in overweight patients [15, 16]. A major goal of weight management is to improve cardiovascular risks so that the overall obesity-related morbidity and mortality can be reduced. Therefore, drugs for obesity are expected to demonstrate these additional benefits [17].

While there are many factors which contribute to obesity, the balance between calorie intake and energy expenditure is crucial in determining a person's weight. Drug treatment of obesity can be classified into three groups based on different mechanisms of action: drugs that reduce food intake; drugs that interfere with fat absorption; and drugs that increase energy expenditure and thermogenesis. Table 1 is a summary of the most commonly used anti-obesity medications that are currently available.

Table 1.  Commonly used anti-obesity medications
DrugMechanism of actionEffect on weightSide effects
Phentermine [20]Reducing food intake: sympathomimetic amine3.6 kg at 6 monthsHeadache, insomnia, irritability, palpitations and nervousness
Diethylpropion [20]As above3.0 kg at 6 monthsAs above
Fluoxetine [23]Reducing food intake: selective serotonin re-uptake inhibitor4.74 kg at 6 months, and 3.15 kg at 1 yearAgitation, and nervousness
Sibutramine [25]Reducing food intake: combined norepinephrine and serotonin re-uptake inhibitor4.45 kg at 1 yearHeadache, insomnia, dry mouth and constipation
Orlistat [23]Affecting fat absorption: lipase inhibitor2.59 kg at 6 months and 2.89 kg at 1 yearDiarrhoea, flatulence, bloating, abdominal pain and dyspepsia

Drugs that reduce food intake

This class of medication used for weight control acts primarily on neurotransmitters of the central nervous system to reduce food intake [18]. This class of drugs includes noradrenergic drugs, serotonergic drugs, serotonergic and adrenergic drugs, drugs binding to the γ-aminobutyric acid receptors or the cannabinoid receptors, and some peptides that reduce appetite or elicit a feeling of satiety [18].

Noradrenergic drugs release norepinephrine (noradrenaline) or block its uptake into neurons to affect food intake. Norepinephrine is released from stores in the presynaptic vesicles, and then reduces food intake by acting on β-adrenergic receptors in the perifornical hypothalamus [18]. These drugs include phenylpropanolamine, amphetamine, phentermine and diethylpropion. Phenylpropanolamine has been withdrawn because of its association with an increased risk of haemorrhagic stroke [19]. Amphetamine is potentially addictive and is therefore not recommended for the treatment of obesity [20]. Phentermine and diethylpropion, which stimulate the release of norepinephrine, are sympathomimetic amines like amphetamine. However, unlike amphetamine, they have little or no effect on dopamine release at the synapse [20]. In a meta-analysis of anti-obesity drugs, phentermine used in combination with lifestyle interventions was found to be associated with a modest pooled mean weight loss of 3.6 kg (95% confidence interval (CI), 0.6, 6.0 kg) at 6 months, which was statistically significant. The pooled mean weight loss was 3.0 kg (95% CI, −1.6, 11.5 kg) for diethylpropion-treated patients, which was of borderline statistical significance [21]. In a comparative study of phentermine and diethylpropion in the treatment of obese patients in general practice, there was significantly greater weight loss in patients treated with phentermine for 12 weeks [22]. In addition, there were significant reductions in blood pressure and heart rate in the phentermine group and of heart rate in the diethylpropion group, which were more likely to be secondary to weight loss than a direct drug effect [22]. Common side effects of phentermine and diethylpropion include headache, insomnia, irritability, palpitations, and nervousness [10]. However, there are limited efficacy and safety data for phentermine and diethylpropion. Their approval for the management of obesity is restricted to short-term use (<12 weeks).

Dexfenfluramine and fenfluramine are serotonergic medications, which act predominantly by releasing serotonin (5-HT) to elicit a feeling of satiety and reduce food intake, especially fat intake [23]. These two drugs have been associated with primary pulmonary hypertension and heart valve damage, which resulted in their withdrawal by the United States Food and Drug Administration (USFDA) [19].

Fluoxetine, a drug approved for use in the treatment of depression, is a selective serotonin re-uptake inhibitor. It has been widely used clinically for the treatment of depression without being associated with pulmonary hypertension or cardiac valvular damage. A number of short-term clinical trial studies of fluoxetine treatment reported that it produced a dose-related decrease in body weight [24]. The pooled weight loss due to fluoxetine was 4.74 kg at 6 months and 3.15 kg at 12 months [24]. Fluoxetine has not yet been approved for use in the treatment of obesity.

The serotonergic and adrenergic drug sibutramine was approved by the USFDA in 1997 and has become widely used. Sibutramine works predominantly through its two pharmacologically active metabolites, N-desmethyl and N-bisdesmethyl sibutramine, which suppress appetite, elicit a feeling of satiety, and increase thermogenesis by inhibiting serotonin and norepinephrine re-uptake [25]. Sibutramine is one of only two medications currently approved for long-term (>12 months) management of obesity [19]. The efficacy of sibutramine in patients who had a BMI of 25 kg m−2 or greater was addressed in a meta-analysis, which showed that sibutramine was more effective than placebo in promoting weight loss in overweight and obese adults at all time points assessed, with a mean difference in weight loss of 4.45 kg at 12 months [26]. However, weight was regained after treatment cessation in studies of 24 weeks or less in duration [27]. A 12-month study showed that sibutramine improved biochemical risk factors associated with obesity, such as plasma triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), glucose and insulin [25]. In addition, sibutramine caused a small and sustained increase in blood pressure (a mean of 2 mm Hg increase in both diastolic and systolic blood pressure at doses of 10–15 mg once a day) and heart rate [25]. The increase in blood pressure was more pronounced in patients who were less than 44 years of age and with an initial body weight of 92 kg or greater [25]. However, there were other placebo-controlled trials of sibutramine that did not show an increase in blood pressure in either normotensive individuals or hypertensive patients [28]. In addition, a recent 6 month study showed that compared with the verapamil sustained release/trandolapril combination, the sibutramine/verapamil sustained release/trandolapril combination in obese hypertensive patients significantly reduced their blood pressure and improved anthropometric and metabolic variables such as total cholesterol, HDL-C and triglycerides [29]. Therefore, the effect of sibutramine on the sympathetic nervous system may be more complex than previously believed. Heusser and colleagues studied the influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects [30]. Their data support the concept that the peripheral stimulatory effect of sibutramine is counteracted by a central inhibitory effect on the sympathetic nervous system. The balance between peripheral and central changes in sympathetic activity determines the net blood pressure response, which may differ between patient populations. It was thought that sibutramine should not be used in patients with coronary heart disease, congestive heart failure, cardiac arrhythmias, uncontrolled high blood pressure or history of stroke. However, data from the 6-week single-blind period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial suggest that sibutramine is efficacious, tolerable and safe in a high-risk population with cardiovascular disease [31]. The SCOUT trial is a randomized, double-blind and placebo-controlled study of sibutramine. A total of 10 742 patients with cardiovascular disease, hypertension or type 2 diabetes received single-blind sibutramine in the 6-week lead-in period. This 6-week treatment caused a significant reduction of body weight (median 2.2 kg), waist circumference (mean 2.0 cm), systolic blood pressure (mean 3.0 mmHg), diastolic blood pressure (1.0 mmHg), and pulse rate (mean 1.5 beats min−1) [31]. The most common side effects of sibutramine include headache, insomnia, dry mouth and constipation [25]. Sibutramine does not have the potential for abuse that is characteristic of amphetamine [25]. Thus far, there are no reported increases in pulmonary hypertension or heart valve damage associated with the use of sibutramine. However, more long-term clinical data are needed to establish the drug's safety and efficacy.

There is currently a novel class of drugs aimed at tackling obesity and related metabolic and cardiovascular disorders by selectively antagonizing the cannabinoid type 1 receptor (CB1) [32]. In April 2006, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) recommended the approval of rimonabant, the first drug of this class, as an adjunct to diet and exercise in treating obesity. However, in October 2008, despite the extensive clinical trial data, EMEA announced that it has recommended suspension of rimonabant because of its psychiatric side effects [33]. The endocannabinoid system plays an important role in the physiological regulation of food intake, energy balance, as well as lipid and glucose metabolism [34]. Endocannabinoids act as endogenous ligands for two types of G protein-coupled cannabinoid receptors, CB1 and CB2[35]. The CB1 receptor is located in several areas of the brain and in peripheral tissues important in glucose and lipid metabolism, such as adipose tissue, the gastrointestinal tract, the liver and muscle. The CB2 receptor is located in the immune system. Rimonabant acts by selectively blocking CB1 receptors in the brain and in the periphery. So far, there have been four large randomized clinical trials that studied the use of rimonabant (Table 2) [35–38]. The Rimonabant In Obesity (RIO) Europe trial and the RIO-North America trial involved patients with obesity. The RIO-Lipids and RIO-Diabetes trials involved patients with dislipidaemia and type 2 diabetes, respectively. All these clinical trials of rimonabant showed similar effects of the drug on weight loss and cardiovascular risk factors, including HDL-C, triglyceride and prevalence of the metabolic syndrome [35–38]. In addition, data from the RIO-Lipids trial showed that about half of the effect of rimonabant on HDL-C and triglyceride was independent of weight loss, which might be related to the increased expression of adiponectin [37]. Further studies are needed to elucidate the mechanisms responsible for the change in lipid profile. However, it has been found that the rate of psychiatric side effects, including anxiety and depression, was high. In the same four studies, adverse psychiatric events were observed in 26% of the patients on treatment with rimonabant compared with 14% of those on placebo [39].

Table 2.  Large clinical trials investigating the effect of 1-year treatment with rimonabant*
 RIO-Europe[35]RIO-North American[36]RIO-Lipids[37]RIO-Diabetes[38]
  1. RIO, Rimonabant In Obesity; WC, waist circumference; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides; *Each study compared the effects of rimonobant 20 mg daily vs rimonobant 5 mg daily vs placebo.

Number of patients1507304510361047
DescriptionBMI ≥ 30 kg m−2 or BMI > 27 kg m−2 with hypertension or dyslipidaemiaBMI ≥ 30 kg m−2 or BMI > 27 kg m−2 with hypertension or dyslipidaemiaBMI between 27 to 40 kg m−2 with untreated dyslipidaemiaBMI between 27 to 40 kg m−2 with type 2 diabetes which was inadequately controlled
Placebo-substracted improvement in outcome with rimonobant 20 mg daily (95% confidence interval)*
Weight (kg)4.8 (3.9, 5.7)4.7 (4.1, 5.4)5.4 (4.6, 6.2)3.9 (3.2, 4.6)
WC (cm)4.1 (3.1, 5.1)3.6 (2.9, 4.3)4.7 (3.7, 5.7)3.3 (2.4, 4.1)
HDL-C (%)9 (6, 12)7 (6, 9)8 (5, 11)8 (6, 11)
TG (%)15 (10, 12)13 (9, 18)12 (6, 19)16 (10, 23)

Drugs which interfere with fat absorption

Orlistat is a reversible gastrointestinal lipase inhibitor which inactivates hydrolyzation of dietary fat and prevents absorption of dietary fat by approximately 30%, thus reducing the calorie intake of the patient [40, 41]. Orlistat is the medication, other than sibutramine, currently approved for the long-term management of obesity [19]. In February 2007, a reduced-strength version of orlistat was approved for over-the-counter use by USFDA [42]. A meta-analysis of 29 studies of orlistat for weight loss in adults reported that the pooled mean weight loss was 2.59 kg at 6 months and 2.89 kg at 12 months [24]. A number of clinical trials including the 4-year XENical in the prevention of diabetes in obese subjects (XENDOS) study demonstrated that orlistat-treated patients had statistically significant reductions in waist circumference, total and LDL-C, blood pressure and improvements in blood glucose concentrations and insulin resistance when compared with patients on placebo and diet only [43–46]. A 54-week randomized controlled trial assessed the effect of orlistat on weight and body composition in obese adolescents aged 12–16 years [47]. At the end of this study, the BMI of participants treated with orlistat had decreased from baseline by 0.55 with orlistat but increased by 0.31 with placebo (P = 0.001). Therefore, it showed that orlistat used in combination with diet, exercise and behavioural modification, resulted in statistically significant improvement in weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population appeared to be safe. However, a recent randomized, double-blind, placebo-controlled trial of orlistat in adolescents did not show any significant effects of orlistat on weight loss at 6 months [48]. Therefore, more clinical studies should be performed to determine the efficacy and safety of orlistat in adolescents. The most common side effects of orlistat include diarrhoea, flatulence, bloating, abdominal pain and dyspepsia, which are related to the unabsorbed fat in the intestine [10]. Patients on orlistat should receive adequate vitamin supplementation because long-term decrease in fat absorption can result in a deficiency of the fat-soluble vitamins (vitamin A, D, E and K).

Drugs which increase energy expenditure and thermogenesis

Ephedrine and caffeine belong to this category. One long-term placebo-controlled clinical trial with ephedrine, caffeine or their combination showed that the combination of ephedrine and caffeine had greater effect on weight loss than either when used alone. These substances are contained in some health supplements. However, the USFDA has not approved the combination of ephedrine and caffeine as a weight-reducing treatment [23].

The future of anti-obesity medications

Currently, there are more than 30 drugs in various stages of research and development [49]. There are many new drugs at different stages of clinical trials, including APD-365, CD-945,598, MK-0364, Qnexa (phentermine and topiramine), Contrave (bupropion and naltrexone), ATL-962, GT 389–255, AOD9604, leptin, peptide YY(3–36), TM30338, and pramlintide (Table 3) [50–52]. It is hoped that some of these will eventually prove to be efficacious and safe in the treatment of obesity.

Table 3.  Mechanisms of potentially new anti-obesity medications in clinical trials [50–52]
TreatmentMechanism of action
Central mechanism
1APD-356A selective agonist of 5-HT2c receptor in the hypothalamus
2CP-945,598CB1 receptor antagonist
3MK-0364CB1 receptor antagonist
4Phentermine + topiramine (Qnexa)A combination of phentermine and topiramine, which reduces the frequency of binge eating
5Bupropion + naltrexone (Contrave)A combination of bupropion, a dopamine and norepinephrine re-uptake inhibitor, and naltrexone, an opioid-receptor antagonist
Peripheral mechanism
1Lipase inhibitor 
ATL-962 GT 389–255Inhibiting absorption of dietary fat in the gastrointestinal tract A combination of a lipase inhibitor and a polymer designed to bind undigested triglycerides
2Lipid metabolism modulator 
AOD9604A synthetic fragment of human growth hormone, increasing fat loss and decreasing the synthesis of new fat
1LeptinInhibiting synthesis and release of appetite-stimulating factors, such as the hypothalamic neuropeptide Y; increasing the activity of appetite-reducing neuropeptides, such as α-melanocyte-stimulating hormone
Gut hormone
1Glucagon-like peptide-1 (GLP-1)Reducing appetite via the GLP-1 receptor in the central nerve system; lowering blood glucose through stimulated insulin secretion, inhibited glucagons secretion, and delayed gastric emptying
2Peptide YY(3–36)Synthetic form of hormone peptide YY(3–36), which reduces appetite through the Y2 receptors in the hypothalamic arcuate nucleus
3TM30338Agonist of both the Y2 and Y4 receptors, which reduce appetite
Pancreatic hormone
1PramlintideA synthetic version of the pancreatic hormone amylin, reducing appetite and enhancing satiety through delayed gastrointestinal motility

Glucagon-like peptide-1 (GLP-1) is an incretin, a hormone secreted in response to glucose in the gut that slows down gastric emptying and stimulates insulin secretion [50]. Although it causes nausea and needs to be injected, it reduces appetite and facilitates weight loss. Gliptins increase the circulating concentration of incretins by inhibiting dipeptidyl peptidase IV (DPP-4), the enzyme that breaks down incretins and other peptides [53]. Their oral route of administration is an advantage. Exenatide is an approved anti-diabetic agent mimicking the effects of GLP-1 [54]. It has been known to induce weight loss [54]. Liraglutide, which is a GLP-1 analogue on trial, was found to improve glucose control and increase weight loss in patients with type 2 diabetes [55]. These drugs acting on the incretin system are at present not indicated for obesity but for glycaemic control in patients with type 2 diabetes who are already on metformin therapy.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Pharmacological treatment for obesity
  5. Conclusion
  6. Competing interests

Pharmacological treatment for obesity decreases body weight and is expected to reduce the health risks associated with obesity. Most of the anti-obesity medications that are currently available are approved by the USFDA for short-term use only. Sibutramine and orlistat are the only two medications approved for long-term use. The longest duration of treatment in clinical trials is 2 years for sibutramine and 4 years for orlistat. These trials could only provide limited information on the long-term morbidity and mortality. Therefore, long-term clinical studies are needed. The safety and efficacy of these drugs should also be evaluated in children, adolescents and the elderly because obesity is a problem that affects all ages. Furthermore, anti-obesity drugs should be explored for synergistic effects when used in combination.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Pharmacological treatment for obesity
  5. Conclusion
  6. Competing interests
  • 1
    Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289: 769.
  • 2
    James PT, Rigby N, Leach R. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004; 11: 38.
  • 3
    Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006; 295: 154955.
  • 4
    Hubert H, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67: 96877.
  • 5
    Lean ME, Han TS, Seidell JC. Impairment of health and quality of life in people with large waist circumference. Lancet 1998; 351: 8536.
  • 6
    Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001; 345: 7907.
  • 7
    Ford ES, Mokdad AH, Giles WH. Trends in waist circumference among U.S. adults. Obes Res 2003; 11: 122331.
  • 8
    World Health Organization. Obesity: Preventing and managing the global epidemic. (Report of a WHO Consultation on Obesity, Geneva, 3–5 June 1997). Geneva: WHO, 1998.
  • 9
    Baumgartner RN, Heymsfield SB, Roche AF. Human body composition and the epidemiology of chronic disease. Obes Res 1995; 3: 7395.
  • 10
    Snow V, Barry P, Fitterman N, Qaseem A, Weiss K. Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005; 142: 52531.
  • 11
    Bravata DM, Sanders L, Huang J, Krumholz HM, Olkin I, Gardner CD, Bravata DM. Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 2003; 289: 183750.
  • 12
    Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003; 348: 207481.
  • 13
    Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low carbohydrate,ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004; 140: 76977.
  • 14
    Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, Hesson LA, Osei SY, Kaplan R, Stunkard AJ. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353: 211120.
  • 15
    Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord 1992; 16: 397415.
  • 16
    Van Gaal LF, Wauters MA, De Leeuw IH. The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes Relat Metab Disord 1997; 21: s59.
  • 17
    Leung WYS, Thomas GN, Chan JCN, Tomlinson B. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clinical Therapeutics 2003; 25: 5880.
  • 18
    Bray GA. Drug insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 8995.
  • 19
    Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf 2006; 29: 277302.
  • 20
    Bray GA. Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med 1993; 119: 70713.
  • 21
    Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord 2002; 26: 26273.
  • 22
    Valle-Jones JC, Brodie NH, O'Hara H, O'Hara J, McGhie RL. A comparative study of phentermine and diethylpropion in the treatment of obese patients in general practice. Pharmatherapeutica 1983; 3: 3004.
  • 23
    Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 5818.
  • 24
    Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, Hilton L, Suttorp M, Solomon V, Shekelle PG, Morton SC. Meta-analysis pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 53246.
  • 25
    Nisoli E, Carruba MO. An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. Obes Rev 2000; 1: 12739.
  • 26
    Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004; 164: 9941003.
  • 27
    McNeely W, Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs 1998; 56: 1093124.
  • 28
    Jordan J, Scholze J, Matiba B, Wirth A, Hauner H, Sharma AM. Influence of sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obes Relat Metab Disord 2005; 29: 50916.
  • 29
    Nakou E, Filippatos TD, Liberopoulos EN, Tselepis AD, Kiortsis DN, Mikhailidis DP, Elisaf MS. Effects of sibutramine plus verapamil sustained release/trandolapril combination on blood pressure and metabolic variables in obese hypertensive patients. Expert Opin Pharmacother 2008; 9: 162939.
  • 30
    Heusser K, Tank J, Diedrich A, Engeli S, Klaua S, Krüger N, Strauss A, Stoffels G, Luft FC, Jordan J. Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects. Clin Pharmacol Ther 2006; 79: 5008.
  • 31
    Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A, Sharma A, Brisco W, Deaton R, Shepherd G, James P; SCOUT Investigators. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial. Eur Heart J 2007; 28: 291523.
  • 32
    Pagotto U, Pasquali R. Fighting obesity and associated risk factors by antagonizing cannabinoid type 1 receptors. Lancet 2005; 365: 13634.
  • 33
    European Medicines Agency. The European Medicines Agency recommends suspension of the marketing authorization of Acomplia. [press release] Oct 23, 2008. Available at: (Doc. Ref.: EMEA/CHMP/537777/2008).
  • 34
    Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004; 3: 77184.
  • 35
    Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rösser S, for the RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 138997.
  • 36
    Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, for RIO-North America Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006; 295: 76175.
  • 37
    Despres JP, Golay A, Sjostrom L, Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353: 212134.
  • 38
    Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF; RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006; 368: 166072.
  • 39
    Samat A, Tomlinson B, Taheri S, Thomas GN. Rimonabant for the treatment of obesity. Recent Pat Cardiovas Drug Discov 2008; 3: 18793.
  • 40
    Guerciolini R. Mode of action of orlistat. Int J Obes Relat Metab Disord 1997; 21: s1223.
  • 41
    Zhi J, Melia AT, Guerciolini R, Chung J, Kinberg J, Hauptman JB, Patel IH. Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers. Clin Pharmacol Ther 1994; 56: 825.
  • 42
    US Food and Drug Administration. FDA approves orlistat for obesity. [press announcement] Febuary 7, 2007. Available at
  • 43
    Torgerson JS, Hauptman J, Boldrin MN, 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 2004; 27: 15561.
  • 44
    Schneider R, Golzman B, Turkot S, Kogan J, Oren S. Effect of weight loss on blood pressure, arterial compliance, and insulin resistance in normotensive obese subjects. Am J Med Sci 2005; 330: 15760.
  • 45
    Beck-da-Silva L, Higginson L, Frasser M, Williams K, Haddad H. Effect of orlistat in obese patients with heart failure: a pilot study. Congest Heart Fail 2005; 11: 11823.
  • 46
    Shi YF, Pan CY, Hill J, Gao Y. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed type 2 diabetes. Diabetic Med 2005; 22: 173743.
  • 47
    Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005; 293: 287383.
  • 48
    Maahs D, De Serna DG, Kolotkin RL, Ralston S, Sandate J, Qualls C, Schade DS. Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocr Pract 2006; 12: 1828.
  • 49
    Hirsch B. Review of anti-obesity medications currently under development. Am J Bar Med 2000; 15: 1623.
  • 50
    Cooke D, Bloom S. The obesity pipeline: current strategies in the development of anti-obesity drugs. Nat Rev Drug Discov 2006; 5: 91931.
  • 51
    Fong TM, Guan XM, Marsh DJ, Shen CP, Stribling DS, Rosko KM, Lao J, Yu H, Feng Y, Xiao JC, Van der Ploeg LH, Goulet MT, Hagmann WK, Lin LS, Lanza TJ Jr, Jewell JP, Liu P, Shah SK, Qi H, Tong X, Wang J, Xu SS, Francis B, Strack AM, MacIntyre DE, Shearman LP. Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), in rodents. J Pharmacol Exp Ther 2007; 321: 101322.
  • 52
    Melnikova I, Wages D. Anti-obesity therapies. Nat Rev Drug Discov 2006; 5: 36970.
  • 53
    Bonora E. Antidiabetic medications in overweight/obese patients with type 2 diabetes: drawbacks of current drugs and potential advantages of incretin-based treatment on body weight. Int J Clin Pract Suppl 2007; 154: 1928.
  • 54
    Palamara KL, Mogul HR, Peterson SJ, Frishman WH. Obesity: new perspectives and pharmacotherapies. Cardiol Rev 2006; 14: 23858.
  • 55
    Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide vs glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomized, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009; 373: 47381.