Obesity –Pharmacological treatments

Dietary management –A low energy,low fat diet is the most effective lifestyle intervention for weight loss Exercise –Encourage adults to take part in moderate physical activity Behavioural modification Drugs –Considered as an addition to the above approaches to help tackle obesity Orlistat (Xenical) Sibutramine (Reductil) Rimonabant (Acomplia) Management of obesity

Orlistat works by preventing the absorption of fat from the intestinal tract- producing an approx100 kcal per day deficit Produces a weight loss over placebo of about 2-5kg on average Proportion who lost 10% or more of their initial weight at 12 months (full support and advice provided in trials) –Orlistat % –placebo - 8.3%, (P < 0.001). Adverse effects: –Oily spotting –Flatulence –Fatty oily stools –Faecal urgency People taking Orlistat may require vitamin supplementation Orlistat- Clinical Evidence, Issue 4 Dec 2000:

Orlistat - NICE Clinical guidelines 43 Prescribe only as part of an overall plan for managing obesity in adults who have: – a BMI of 28.0 kg/m2 or more with associated risk factors, or – a BMI of 30.0 kg/m2 or more. Continue treatment for longer than 3 months only if the person has lost at least 5% of their initial body weight since starting drug treatment (less strict goals may be appropriate for people with type 2 diabetes). Continue for longer than 12 months (usually for weight maintenance) only after discussing potential benefits and limitations with the patient. Co-prescribing with other drugs for weight reduction is not recommended.

Sibutramine is a centrally acting agent shown to affect weight loss by enhancing satiety. In two 12 months studies, mean weight loss was: –Sibutramine kg –placebo kg. In both trials, weight loss stabilised after 6 months of Sibutramine. Adverse effects –Increase in blood pressure –Constipation,Nausea & Dry mouth Recommended “Only as part of a long-term integrated therapeutic approach for weight reduction under the care of a physician experienced in the treatment of obesity” Sibutramine Clinical Evidence, Issue 4 Dec 2000:

Prescribe only as part of an overall plan for managing obesity in adults who have: – a BMI of 27.0 kg/m2 or more and other obesity- related risk factors such as type 2 diabetes or dyslipidaemia, or – a BMI of 30.0 kg/m2 or more. Prescribe only if there are adequate arrangements for monitoring both weight loss and adverse effects (specifically pulse and blood pressure). Continue treatment for longer than 3 months only if the person has lost at least 5% of their initial body weight since starting drug treatment (less strict goals may be appropriate for people with type 2 diabetes) Treatment is not recommended beyond the licensed duration of 12 months. Co-prescribing with other drugs aimed at weight reduction is not recommended. Sibutramine - NICE guidelines

Rimonabant- NICE review in progress Rimonabant is a cannabinoid receptor antagonist licensed as an adjunct to diet and exercise for obese or overweight patients with associated risk factors. Mean weight reduction of 4.7kg (95%Cl 4.1 to 5.3 p<0.0001) 1 in every 15 patients treated dropped out due to side effects (number needed to harm [NNH] = 15). Depression and anxiety Patients with psychiatric illnesses were excluded from trials Still ▼ requiring close monitoring of side effects Not currently approved for prescribing in the PCT

Meta-Analysis– long term pharmacotherapy for obese and overweight patients–BMJ online15 th Nov Orlistat reduced weight by 2.9kg (95% CL,2.5kg-3.2kg) Sibutramine by 4.2kg (3.6kg to 4.7 kg) Rimonabant 4.7 kg (4.1 kg to 5.3kg)

Side effects seen in trials

Drug treatment should be considered for adults: only after dietary and exercise advice have been started and evaluated for patients who have not reached their target weight or have reached a plateau These recommendations update the NICE technology appraisals on orlistat and sibutramine Management: drug treatment for adults- NICE CG 43

NICE guidelines on drug treatments Before deciding to start treatment, and choosing the drug, discuss with the patient the potential benefits and limitations, including the mode of action, adverse effects and monitoring requirements,and their potential impact on the patient’s motivation. When prescribing, make arrangements for appropriate healthcare professionals to offer information, support and counselling on additional diet, physical activity and behavioural strategies. Give information on patient support programmes. Follow the drug’s summary of product characteristics.

Continued prescribing and withdrawal NICE Clinical Guidelines 43 Review regularly, to monitor the effect of drug treatment, and to reinforce lifestyle advice and need for adherence. Drug treatment may be used to help people to maintain weight loss, as well as to continue to lose weight. Consider withdrawing drug treatment if the person does not lose enough weight Consider less strict goals for people with type 2 diabetes, because they may lose weight more slowly. Agree goals with the person and review regularly. If concerned about micronutrient intake, consider giving a supplement providing the reference nutrient intake for all vitamins and trace elements, particularly for vulnerable groups such as older people, who may be at risk of malnutrition. If withdrawing a person’s drug treatment, offer support to help maintain weight loss because their self-confidence and belief in their ability to make changes may be low.

Cost of these products

Spend on Obesity Treatments in Derbyshire County PCT

Results of Local Audits Audits have been undertaken in our local GP practices against the NICE standards Results showed 73% of orlistat prescribing and 40% of sibutramine prescribing was outside of NICE guidance That is; treatment continued beyond three months when patients had not achieved a least 5% weight loss

Conclusions Drugs do help some people achieve better weight loss, each drug resulted in <5kg weight reduction compared with placebo. –But most trials on non elderly and white so extrapolation to other populations should be made with caution They should be integrated with other approaches that address the patients motivation and prevent the idea that obesity can be fixed by a medicines and undermine ‘healthy living’messages Drugs to be used in line with NICE guidance