• Home
• Events
• Medicines Management
• Evidence Based Therapeutics
• Associate Programme
• Policy into Practice
• Supporting Prescribers

The drug management of obesity
Volume 18 Number 5
April 2008

Introduction

The detrimental effects of obesity on health are well known, yet its incidence is continuing to rise. Nearly a quarter of all adults in England are obese and the government has predicted that 33% of men and 28% of women will be obese by 2010.^1,2 Obesity has also reached 'epidemic' proportions in children. This is particularly concerning, especially as excess weight in the early years has been associated with obesity in adulthood.³ In England, nearly a third of children aged two to 15 years are either overweight or obese.¹

Obesity occurs when a person gains weight to the point that it seriously endangers their health.⁴ Body mass index (BMI) is usually used for defining overweight or obesity in adults (Panel).⁵ However, BMI needs to be interpreted with caution as it is not a direct measure of adiposity. For adults, assessment of the health risks associated with being overweight and obese should be based on a combination of BMI and waist circumference. The National Institute for Health and Clinical Excellence (NICE) obesity clinical guideline contains a useful risk assessment table that can be used when advising patients on the impact these measurements have on their risk of developing long-term health problems (Panel).⁵

Several causes of overweight and obesity have been suggested from observational studies (e.g. sedentary lifestyle, consumption of energy-dense foods, marketing of fast-food outlets, adverse socioeconomic conditions, etc.).³ As a result, the government has developed a programme of initiatives to address various social, behavioural and societal issues.³ Even so, it should not be forgotten that, fundamentally, being overweight and obese is caused by consuming more calories than are expended.⁴

Why lose weight?

Everyone should aim to maintain or achieve a healthy weight to reduce their risk of diseases associated with overweight or obesity, such as coronary heart disease (CHD), type 2 diabetes, osteoarthritis and some cancers.^5,6 It is important to remember, however, that the risks of specific diseases from being overweight or obese will depend on individual factors, such as co-morbidities, age, sex, smoking, muscular build, ethnic origin, etc.^5,7 For example, an analysis of 3,457 patients from the Framingham Heart Study found that, at age 40, obese female smokers lost 13.3 years of life expectancy and obese male smokers lost 13.7 years, compared with normal-weight non-smokers.⁷ At the same age, obese female non-smokers lost 7.1 years and obese male non-smokers lost 5.8 years compared with normal weight non-smokers.⁷ Healthcare professionals should use their clinical judgement to decide when to measure someone's height and weight, and when considering risk factors in certain people.⁵ The psychological and social burdens of obesity should also not be underestimated. Low self esteem, reduced mobility and, generally, a poorer quality of life are common experiences of obese people.⁴

What is the best way to lose weight?

NICE emphasises the importance of adopting an individualised approach to weight loss. The approach taken should take into account patients' preferences, their social circumstances, previous treatments tried, and their risk of disease along with any co-morbidities already present. Lifestyle changes, mainly based around improvements in diet and physical activity, are the mainstay of obesity management, and these should be continued even when drugs are required (Panel).⁵ From a public health perspective, it may be helpful to encourage people to start making small manageable changes to their lifestyles by moving a little more and eating a little less.⁸ This may be more helpful than attempting to radically change diet and exercise initially.

Realistic targets for adults who wish to lose weight are usually to aim to lose 5-10% of their original weight, with a maximum weekly weight loss of 0.5 to 1 kg. To lose weight, total energy intake should be less than expenditure. For sustainable weight loss, diets with a 600kcal/day deficit or those that reduce calories by lowering fat content, in combination with expert support and intensive follow-up, are recommended. Adults should also be encouraged to undertake at least 30 minutes of at least moderate-intensity physical activity on five or more days a week. Weight management programmes to improve people's lifestyles should be based on several interventions and include strategies to change behaviour. The NICE clinical guideline on obesity contains more information about such lifestyle and behavioural approaches to weight loss, including what to tell patients, and best practice standards for weight loss programmes and diets.⁵ In addition, it might be helpful to refer to the NICE public health guidance on methods to increase physical activity.⁹

Back to top

When should drugs be used?

Anti-obesity drugs should be considered only after dietary, exercise and behavioural approaches have been started and evaluated.⁵ Adding drug treatment to lifestyle approaches can be considered for patients who have not reached their target weight loss, or for those whose weight has reached a plateau after dietary, physical activity and behavioural changes alone.⁵ Generally, drug treatment may be considered for overweight or obese people who have co-morbidities (e.g. type 2 diabetes) and for obese people without co-morbidities who have a BMI >35kg/m² (i.e. obesity class II) (Panel). However, individual agents should be given within their licensed indications,⁵ which differ slightly from this (see below). Referral to a specialist might be necessary for certain patients e.g. if BMI >50kg/m² or if the underlying causes of obesity need to be assessed (see NICE guideline for further details on who to refer).⁵ None of the drugs has been studied sufficiently in children or elderly

patients.^10-12 NICE has given guidance on the cautious use of orlistat and sibutramine in certain children aged >12 years within a specialist paediatric setting.⁵ However, these drugs are specifically not indicated for children in their product licenses.^10,11

Orlistat, sibutramine and rimonabant^▼ are currently available for treating overweight and obesity. Orlistat is a gastrointestinal (GI) lipase inhibitor which prevents absorption of around 30% of dietary fat.^10,13 Sibutramine, a monoamine-reuptake inhibitor, suppresses appetite by inhibiting serotonin and noradrenaline uptake.^11,13 Rimonabant^▼, which was launched in 2006, is a selective cannabinoid (CB1) receptor blocker.^12,13 The endocannabinoid system is associated with energy balance, glucose and lipid metabolism, body weight, and intake of palatable, sweet or fatty foods.¹²

Orlistat, sibutramine and rimonabant^▼ are licensed for use in obese adults who have a BMI of 30 kg/m² or more; and in overweight adults with associated risk factors (e.g. type 2 diabetes or dyslipidaemia) who have a BMI of 28kg/m² or more (orlistat), or a BMI of 27kg/m² or more (sibutramine), or a BMI more than 27kg/m² (rimonabant^▼).^5,10-12

Use of orlistat and sibutramine is discussed in the NICE clinical guideline on obesity that was published in 2006.⁵ Guidance on the use of rimonabant^▼ is being addressed by a NICE technology appraisal that is underway and is due to be published in May 2008 (see www.nice.org.uk).

About one million prescription items for obesity were dispensed in 2007, more than eight times the amount prescribed in 1999.^1,14 Orlistat accounted for about 67% of prescriptions, sibutramine for 24% and rimonabant^▼ for 9%.¹⁴

How effective are these drugs?

In clinical trials, patients taking drug therapy in addition to lifestyle changes (which includes a hypocaloric diet) lose an average of about 3 to 5kg more weight than with placebo in the first year.¹⁵ Some people will lose more weight than this, whilst some may not lose any weight at all or might even gain weight. When treatment is continued during the second year, drug treatment can help to maintain the initial weight loss seen, even if patients regain some weight.¹⁵ However, obesity is a long-term problem. We are not aware of any strong evidence showing that continued treatment with anti-obesity drugs over several years leads to additional weight loss beyond that seen in the first year. For rimonabant^▼ and sibutramine, the longest duration of fully published randomised controlled trials (RCTs) is currently only two years, and for orlistat, it is four years.^15,16 In addition, treatment with sibutramine is not recommended beyond the licensed duration of one year.^5,11 The product licence for rimonabant^▼ states that the safety and efficacy of rimonabant^▼ have not been evaluated beyond two years.¹² A maximum duration of treatment with orlistat is not specified.¹⁰

Unfortunately, RCTs of anti-obesity drugs commonly have dropout rates of 30 to 40%.¹⁵ In addition, published long-term morbidity and mortality studies are lacking for anti-obesity drugs. However, there is RCT evidence showing that orlistat reduces the incidence of type 2 diabetes (see details of the XENDOS trial below¹⁷) and outcome studies are underway for both sibutramine and rimonabant^▼ (see below).^18,19

Most RCTs of anti-obesity drugs have assessed weight loss as the primary outcome and various cardiovascular (CV) risk factors, such as changes in blood lipids, blood pressure (BP), glycosylated haemoglobin (HbA_1c), waist circumference, etc. as secondary outcomes.¹⁵ The weight loss figures quoted earlier relate to the average weight loss. The European Medicines Agency (EMEA) recommends that the primary outcome of anti-obesity drug studies should include at least a 10% reduction of baseline weight, which is also statistically significantly greater than that associated with placebo.²⁰ It also suggests that a further endpoint may be the proportion of people who have more than 10% weight loss at 12 months.²⁰ These figures are more helpful than looking at the average weight loss as they tell us the proportion of people likely to benefit, given that some people will not lose any additional weight at all with these drugs. These data are now available from more recent meta-analyses, as discussed below. (see below).

Several meta-analyses of anti-obesity drugs in overweight and obesity have been published. The most recent was published in the BMJ and included RCTs that compared anti-obesity drugs with placebo in patients who were overweight or obese (mean BMI 35 to 36 kg/m² i.e. class II obesity) for between one and four years.¹⁵ In most studies, patients in both the active and placebo groups were allocated to a standardised low fat, hypocaloric (low energy) diet and encouraged to exercise. It is important to note that, in addition to the high dropout rates, most studies did not describe the randomisation process or mention whether or not allocation was concealed. In addition, none of the studies mentioned blinding of the outcome assessors and secondary outcomes were inconsistently reported.¹⁵ These shortcomings increase the possibility of bias.

Orlistat
The BMJ meta-analysis assessed sixteen RCTs (n=10,631) of orlistat. Nine of these included only high-risk patients (four RCTs were in people with type 2 diabetes; and five RCTs included obese patients with at least one CV risk factor). At one year, patients in the orlistat group lost 2.9kg more of their bodyweight (95% CI 2.5 to 3.2kg) than those on placebo. Also, compared with placebo, 12% (95% CI 9% to 14%; this was an absolute increase) more patients in the orlistat group achieved >10% weight loss.¹⁵ This translates into a number needed to treat (NNT) of eight. i.e. eight patients would need to be treated with orlistat plus lifestyle changes for one year instead of lifestyle changes alone, for one additional patient to lose at least 10% of their baseline bodyweight. Four RCTs looked at weight maintenance in the second year and found that the initial difference in weight loss between orlistat and placebo was maintained, although both groups regained the same amount of weight.¹⁵ These results are consistent with those from previous meta-analyses of orlistat.^6,21

When the meta-analysis looked at secondary endpoint data, it found that taking orlistat was associated with statistically significant reductions in total cholesterol, low density lipoprotein (LDL) cholesterol, BP, fasting plasma glucose, HbA_1C, BMI and waist circumference, although concentrations of high density lipoprotein (HDL) cholesterol were slightly lowered (which is less desirable).¹⁵ It is important to remember that these are all disease-oriented outcomes and may not necessarily translate into an effect on patient-oriented outcomes i.e. showing whether patients will live longer or better.

The XENDOS study has found that orlistat plus lifestyle changes produces a greater reduction in the incidence of type 2 diabetes than lifestyle changes alone.¹⁷ In this RCT, 3,305 patients with a BMI >30kg/m² (mean BMI 37, mean age 43 years, 79% with normal glucose tolerance and 21% with impaired glucose tolerance [IGT]) were randomised to lifestyle changes plus either orlistat or placebo for four years. However, only 52% of the orlistat group and 34% of the placebo group completed treatment. Using an intention to treat analysis, the mean weight loss was 5.8kg with orlistat and 3.0kg with placebo (P<0.001) after four years. At the end of the study, the incidence of type 2 diabetes was 9.0% in the placebo group and 6.2% in the orlistat group (hazard ratio 0.63; 95% CI 0.46 to 0.86; NNT 36). This reduction was primarily due to benefits in the population of patients with IGT.¹⁷ We do not know yet if this reduces the likelihood of morbidity and mortality in the longer-term.

To put the XENDOS study into context, lifestyle changes alone can be particularly effective in reducing the incidence of type 2 diabetes in overweight people with IGT. In one RCT, 522 overweight people with IGT (mean age 55 years, mean BMI 31kg/m²) were assigned to individualised lifestyle counselling aimed at reducing weight, improving diet and increasing exercise, or a control group given general lifestyle advice.²² Individualised lifestyle counselling reduced the proportion of people who progressed from IGT to type 2 diabetes (3% per year in the intervention group vs. 6% per year in the control group), with a strong inverse relationship being seen between the incidence of type 2 diabetes and the achievement of lifestyle goals, such as >5% weight reduction. After four years, the cumulative incidence of type 2 diabetes was 11% (95% CI 6% to 15%) in the intervention group and 23% (95% CI 17% to 29%) in the control group. In absolute terms, the NNT was eight i.e. eight overweight people with IGT would need to undergo individualised lifestyle counselling for four years, to prevent one additional case of type 2 diabetes.²²

Sibutramine
The BMJ meta-analysis assessed 10 RCTs (n=2,623) of sibutramine, two of which were in patients with controlled hypertension, and three of which were in patients with type 2 diabetes.¹⁵ Seven RCTs looked at the effects of sibutramine on weight loss at one year and found that patients lost 4.2kg (95% CI 3.6 to 4.7kg) more than those taking placebo. This is similar to the weight loss seen in previous meta-analyses of sibutramine.^6,16 An additional 18% (95% CI 11% to 25% of patients achieved >10% weight loss at one year compared with placebo (NNT 6).¹⁵

Three RCTs assessed the effects of sibutramine in maintaining weight loss for up to 18 months. The authors found that between 10% and 30% more patients on sibutramine than placebo maintained at least 80% of their initial weight loss (p<0.05 compared with placebo in all three studies). However, it was not possible to combine data from the studies because the definitions of weight maintenance differed.¹⁵

With regard to secondary endpoint data, sibutramine was associated with statistically significant reductions in BMI, waist circumference and triglyceride concentrations, and increased concentrations of HDL cholesterol.¹⁵ There are currently no fully published RCTs of sibutramine on obesity related morbidity and mortality. However, the Sibutramine Cardiovascular OUTcomes Trial (SCOUT) is underway and is expected to report sometime during 2008. This is a three-year multicentre, double-blind, placebo-controlled trial designed to evaluate the potential benefits of weight management with sibutramine on CV outcomes in overweight and obese patients who are at high risk of CV events.¹⁸

Rimonabant^▼
Four RCTs (n=6,635) of rimonabant^▼ in overweight and obesity have been fully published and were included in the BMJ meta-analysis.¹⁵ Of these, one was in patients with dyslipidaemia, one in patients with type 2 diabetes and the other two included patients with dyslipidaemia or hypertension. All the trials assessed the effects of rimonabant^▼ on weight loss at one year and found that, compared with placebo, patients allocated to rimonabant^▼ lost 4.7kg more body weight (95% CI 4.1 to 5.3kg). Also, compared with placebo, an additional 19% (95% CI 15% to 23% of patients achieved >10% weight loss (NNT 5).¹⁵ A similar weight loss was reported in another meta-analysis of rimonabant^▼ that was published around the same time.²³

One RCT (in patients with dyslipidaemia or hypertension) looked at the effects of rimonabant^▼ on weight maintenance at two years and found that, compared with placebo, rimonabant^▼ maintained the weight lost in the first year.¹⁵

Looking at secondary endpoint data, taking rimonabant^▼ is associated with statistically significant reductions in waist circumference, BP and triglyceride concentrations; as well as increases in HDL cholesterol. Statistically significant reductions in fasting blood glucose and HbA_1C concentrations were also seen in the RCT of patients with type 2 diabetes.¹⁵

There are currently no published studies of rimonabant^▼ looking at whether patients are likely to live longer or better with the drug, but the ongoing CRESCENDO study is looking at its effects on myocardial infarction, stroke and CV death over five years. This is due to complete in 2010.¹⁹

Back to top

What are the safety and side effect data?

As might be expected by its mechanism of action, the most troublesome adverse effects associated with orlistat are GI-related. About one in four patients taking orlistat are likely to experience GI side effects and around one in 50 patients are likely to discontinue treatment because of them.¹⁵ Fatty/oily stools, faecal urgency and oily spotting are the most common GI adverse events; with 15 to 30% of patients experiencing each of these effects in most studies.¹⁵ Orlistat should be avoided by patients with cholestasis and chronic malabsorption syndrome, and it is advisable to warn patients that the GI adverse effects will increase if the fat content of their diet increases.¹⁰ Patients may wish to try a vitamin supplement (especially of vitamin D) if there is concern that they might have a deficiency of fat-soluble vitamins.²⁴

Reported systemic adverse effects with orlistat are minimal.¹³ However, taking orlistat can occasionally lead to an increased or unbalanced anticoagulant effect in people taking warfarin. It also reduces the absorption of amiodarone and ciclosporin.¹⁰ Unlike sibutramine and rimonabant^▼, there have been no Medicines and Healthcare products Regulatory Agency (MHRA) safety warnings about orlistat to date.

Insomnia, nausea, dry mouth and constipation have been reported in 7-20% of patients who take sibutramine in RCTs.¹⁵ However, of a potentially more serious nature, sibutramine is associated with increases in heart rate and BP.^11,15,16 Therefore, it should be avoided in CV disease, uncontrolled hypertension and tachycardia,¹¹ which may limit its use in many obese patients. The BMJ meta-analysis reported a mean increase in systolic BP of 1.7mmHg, in diastolic BP of 2.4mmHg and in pulse rate of 4.5 beats per minute at one year.¹⁵   However, BP can increase up to 3mmHg and pulse rate up to 7 beats per minute, and even greater increases cannot be excluded in isolated cases.¹¹ The long-term consequences of these effects on obese patients who are already at increased CV risk are unclear, although sibutramine is currently not licensed for use beyond a year. Publication of the three-year data from SCOUT may help to provide more clarification on this.¹⁸

In 2003, the Committee on Safety of Medicines recommended that, for patients taking sibutramine, BP and pulse should be monitored every two weeks in the first three months, monthly for another three months, and at least every three months thereafter.²⁵ This includes measuring BP and pulse before starting treatment. Sibutramine should be stopped if the resting pulse rises by 10 beats per minute or more, or if blood pressure rises by 10 mmHg or more during the treatment period on two consecutive visits.^11,25 In addition, patients should be told to consult a doctor urgently if symptoms such as progressive dyspnoea, chest pain or ankle oedema occur.²⁵

Because sibutramine acts on the serotonin system, monoamine oxidase inhibitors and serotonergic drugs (e.g. serotonin-reuptake inhibitors) should be avoided in patients taking this drug.^11,13 This might be important when considering several over-the-counter (OTC) products (e.g. St John's Wort).

In RCTs, almost 16% of patients taking rimonabant^▼ stopped treatment because of adverse events, the most common of which were nausea, mood alteration with depressive symptoms, depressive disorders, anxiety and dizziness.¹² Concern over the risk of psychiatric adverse effects has led to a recent warning from the MHRA, followed by updates to rimonabant's summary of product characteristics (SPC)^12,26 In addition, a meta-analysis of the four fully published RCTs has attempted to analyse the risk of such adverse effects with rimonabant^▼.²³

The meta-analysis found that, at one year, more people taking rimonabant^▼ than placebo experienced adverse events (odds ratio [OR] 1.4, P=0.0007). The number needed to harm [NNH] for adverse events was 25, and for serious adverse events (not defined) it was 59 (OR 1.4, P=0.03). If 100 people took rimonabant^▼ (under the same conditions as the studies included in the meta-analysis) four people would experience adverse events (and two of those four people would experience serious adverse events) who would not have done if all had taken placebo. Further analysis found that withdrawals from the study due to depression or anxiety were more likely in patients receiving rimonabant^▼ than placebo (depression: OR 2.5, P=0.01, NNH 49; anxiety: OR 3.0, P=0.03, NNH 166).²³

The BMJ meta-analysis reported similar results with regard to safety, concluding that rimonabant^▼ caused significantly more general and serious adverse effects than placebo, especially of nervous system, psychiatric or GI origins.¹⁵

It is possible that these meta-analyses do not represent the true risk of psychiatric adverse effects with rimonabant^▼ because trials did not report detailed data on the rates of psychiatric adverse effects experienced by participants. Also, obese people often suffer from depression,²³ but patients with clinically significant psychiatric disease or psychological illness were specifically excluded from most of the rimonabant^▼ RCTs.^27,28

In July 2007, the MHRA reported that around one in 10 people taking rimonabant^▼ may experience psychiatric side effects and around 1 in 100 may experience suicidal thoughts. The MHRA warned that rimonabant^▼ must not be used by patients with major depression or those being treated with antidepressants, because of the risk of psychiatric side effects.²⁶ In addition, patients should be told about the need to look out for such symptoms and to seek medical advice immediately if they occur.¹² Since rimonabant is a black triangle ^▼ drug, all suspected adverse reactions should be reported to the MHRA through its Yellow Card Scheme.

How should anti-obesity drugs be used?

NICE emphasises that drugs should be prescribed only as part of an overall plan for managing obesity. This includes having arrangements in place to provide patients with information, support and counselling on additional diet, physical activity and behavioural strategies. Treatment should be reviewed regularly to monitor for effectiveness, adverse effects and adherence, and lifestyle advice should be reinforced at the same time.⁵

NICE recommends that treatment with orlistat or sibutramine for longer than three months should be considered only if the person has lost at least 5% of their initial body weight since starting drug treatment.⁵ Orlistat may be continued for longer than a year, but only after discussing its risks and benefits with the patient. However, sibutramine treatment is not recommended beyond the licensed duration of a year.⁵ Rimonabant's safety and efficacy has not been established beyond its licensed duration of two years.¹² The NICE technology appraisal (in progress) will provide more guidance on how rimonabant^▼ should be used.

Support should be given to patients who withdraw from treatment as they may have low self-confidence, especially if they did not reach their target weight. People with type 2 diabetes may lose weight more slowly and so less strict goals may need to be agreed. It should be remembered that drug treatment can be used to help maintain weight loss as well as to help people to continue to lose weight.⁵ Patients may regain weight once anti-obesity drugs are stopped.

For more comprehensive information on the prescribing details for each drug, including contraindications, precautions, drug interactions and adverse effects, please refer to their individual SPCs.^10,11,12

Conclusion - which drug should be used?

Lifestyle changes are the mainstay of obesity management. For population benefits, it is worth encouraging people to eat a little less and move a little more. When anti-obesity drugs are used in addition to lifestyle measures, they seem to have a modest effect, leading on average to about a 3 to 5kg greater weight loss than placebo plus lifestyle measures at one year. However, obesity is a long-term problem and long-term morbidity and mortality data on these agents are currently limited. Also, no drug is ideal in terms of its safety/tolerability profile. Therefore, the choice of drug used for managing overweight and obesity should be based on a careful consideration of the potential risks and benefits of each agent in individual patients - bearing in mind important safety concerns from the MHRA, NICE guidance, and the licensed recommendations for each drug. Considering each drug in terms of its Safety, Tolerability, Efficacy, Price and Simplicity of use (STEPS) can help prescribers to make an informed decision around which one to use (Table). The results from long-term morbidity and mortality studies of sibutramine and rimonabant^▼, and fully published guidance from NICE on rimonabant^▼, are awaited and may further help to determine the place of each agent in the management of overweight and obesity.

Back to top

References

1. The Information Centre. Statistics on obesity, physical activity and diet: England, January 2008. Accessed from www.ic.nhs.uk/pubs/opadjan08 on 25/02/08
2. Zaninotto P, Wardle H, Stamatakis E, et al, Joint Health Surveys Unit, National Centre for Social Research and Department of Epidemiology and Public Health at the Royal Free and University College Medical School; for the Department of Health. Forecasting obesity to 2010. August 2006. Accessed from: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsStatistics/DH_4138630 on25/02/08
3. Jebb S, Steer T, Holmes C (MRC Human Nutrition Research, Cambridge). The 'healthy living' social marketing initiative: a review of the evidence. March 2007. Accessed from: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_073044 on 25/02/08
4. National Audit Office. Tackling obesity in England. HC 220 Session 2000-2001; 15th February 2001. Accessed from: www.nao.gov.uk/pn/00-01/0001220.htm on 25/02/08
5. National Institute for Health and Clinical Excellence. Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children. Clinical guideline 43, December 2006. Accessed from: www.nice.org.uk/guidance/index.jsp?action=download&o=30365 on 25/02/08
6. Avenell A, Broom J, Brown TJ, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess 2004;8(21):1-465. Accessed from: www.ncchta.org on 25/02/08
7. Peeters A, Barendregt J, Willekens F, et al for NEDCOM, the Netherlands Epidemiology and Demography Compression of Morbidity Research Group. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003;138:24-32. Accessed from: www.annals.org on 25/02/08
8. Lean MEJ. Prognosis in obesity: we all need to move a little more, eat a little less. BMJ 2005;330:1339-40. Accessed from: www.bmj.com on 11/03/08
9. National Institute for Health and Clinical Excellence. Four commonly used methods to increase physical activity: brief interventions in primary care, exercise referral schemes, pedometers and community-based exercise programmes for walking and cycling. Public Health Intervention Guidance no. 2, March 2006. Accessed from: http://www.nice.org.uk/guidance/ index.jsp?action=byID&o=11373 on 25/03/08
10. Xenical Summary of Product Characteristics, May 2006. Accessed from: http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=1746 on 26/02/08
11. Reductil Summary of Product Characteristics, October 2007. Accessed from: http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=14056 on 26/02/08
    12. British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. No. 54. BMJ Publishing Group Ltd and RPS Publishing. September 2007
12. Acompliaq Summary of Product Characteristics, October 2007. Accessed from http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=18283 on 26/02/08
13. Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabantq. Lancet 2007;369:71-7. Accessed from: www.thelancet.com on 26/02/08
14. Business Services Authority; Prescription Pricing Division. National Prescribing data, Jan 2007 to Dec 2007. Accessed from: www.epact.ppa.nhs.uk on 26/02/08
15. Rucker D, Padwal R, Li SK, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 2007;335:1194-9. Accessed from www.bmj.com on 19/02/08 (This paper is based on a recently updated Cochrane review that is currently undergoing peer review)
16. Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004;164:994-1003. Accessed from www.archinternmed.com on 10/03/08
17. Torgerson JS, Hauptman J, Boldrin MN, et al. Xenical in the prevention of diabetes in obese subjects (XENDOS) study. Diabetes Care 2004;27:155-61. Accessed from: http://care.diabetesjournals.org on 26/02/08
18. James WPT. The SCOUT study: risk-benefit profile of sibutramine in overweight high-risk cardiovascular patients. Eur Heart J 2005; 7 (Suppl L):L44-8. Accessed from: http://eurheartj.oxfordjournals.org on 10/03/08.
19. Food and Drug Administration (FDA) Memorandum, Advisory Committee meeting for rimonabantq (ZimultiTM), June 2007. Accessed from: http://www.fda.gov/ohrms/dockets/ac/07/questions/2007-4306q-fda-questionstocommittee-draft.pdf on 12/02/08
20. Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA). Guideline on clinical investigation of medicinal products used in weight control. CPMP/EWP/281/96 Rev. 1. London, June 2006. Accessed from: www.emea.europa.eu/ on 25/08/08
21. Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005;142:532-46. Accessed from www.annals.org on 01/10/07
22. Tuomilehto J, Lindström J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-50. Accessed from: http://content.nejm.org on 26/02/08
23. Christensen R, Kristensen PK, Bartels EM, et al. Efficacy and safety of the weight-loss drug rimonabantq: a meta-analysis of randomised trials. Lancet 2007; 370:1706-13 Accessed from www.thelancet.com on 22/01/08
24. The British National Formulary (BNF 54). BMJ Publishing Group Ltd and RPS Publishing; London. September 2007
25. Committee on Safety of Medicines. Current Problems in Pharmacovigilance; 29. Sept 2003. Accessed from: http://www.mhra.gov.uk/Publications/Safetyguidance/CurrentProblemsinPharmacovigilance/ CON007449 on 26/02/08
26. New advice concerning the use of Acomplia (rimonabantq) for weight loss in patients taking antidepressants or those with major depression. Medicines and Healthcare products Regulatory Agency. July 2007. Accessed from http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&ssDocName=CON2031809&ss SourceNodeId=221&ssTargetNodeId=221 on 22/01/08
27. Curioni C, André C. Rimonabantq for overweight or obesity. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006162. DOI: 10.1002/14651858.CD006162.pub2.
28. Scheen AJ, Finer N, Hollander P, et al. Efficacy and tolerability of rimonabantq in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006;368:1660-72. Accessed from: http://www.thelancet.com/journals/lancet/article/PIIS0140673606695718/abstract on 11/03/08
29. NHS Business Services Authority. Drug Tariff. The Stationery Office; Norwich, March 2008

Back to top

The National Institute for Health and Clinical Excellence (NICE) is associated with MeReC Publications published by the NPC through a funding contract. This arrangement provides NICE with the ability to secure value for money in the use of NHS funds invested in its work and enables it to influence topic selection, methodology and dissemination practice. NICE considers the work of this organisation to be of value to the NHS in England and Wales and recommends that it be used to inform decisions on service organisation and delivery. This publication represents the views of the authors and not necessarily those of the Institute.

NPC materials may be downloaded / copied freely by people employed by the NHS in England for purposes that support NHS activities in England. Any person not employed by the NHS, or who is working for the NHS outside England, who wishes to download / copy NPC materials for purposes other than their personal use should seek permission first from the NPC.
Email: copyright@npc.nhs.uk Copyright 2008

National Prescribing Centre, The Infirmary, 70 Pembroke Place, Liverpool, L69 3GF Tel: 0151 794 8146 Fax: 0151 794 8139