Drugs

Drugs - A huge investment has been made by the pharmaceutical industry in finding drugs for obesity. The side-effect profile has limited the use of many agents, but a few drugs are currently licensed (Box 5.28). There is no role for diuretics, or for thyroxine therapy without biochemical evidence of hypothyroidism.

Orlistat is Drug Obesity

Anti-obesity Drug Reductil Faces a Ban in Europe

Orlistat inhibits pancreatic and gastric lipases andthereby decreases the hydrolysis of ingested triglycerides, reducing dietary fat absorption by ∼30%. The drug is not absorbed and adverse side-effects relate to the effect of the resultant fat malabsorption on the gut: namely, loose stools, oily spotting, faecal urgency, flatus and the potential for malabsorption of fat-soluble vitamins. Orlistat is taken with each of the three main meals of the day and the dose can be adjusted (60–120 mg) to minimise side-effects. Its efficacy is shown in Box 5.29 and Figure 5.13; these effects may be explained because patients taking orlistat adhere better to low-fat diets in order to avoid unpleasant gastrointestinal side-effects. Sibutramine reduces food intake through β1- adrenoceptor and 5-HT 2A/2C (5hydroxytryptamine,serotonin) receptor agonist activity in the central nervous system. 

Weight loss with sibutramine is 3–5 kg better than placebo with 6 months’ therapy and is associated with an improvement in lipid profile (see Box 5.29).Side-effects include dry mouth, constipation and insomnia. Unfortunately, noradrenergic effects of the drug can increase heart rate and blood pressure; these effects are especially undesirable in obese patients. Sibutramine is thus usually second choice after orlistat and cannot be used in those with hypertension or cardiovascular disease. There is insufficient evidence to recommend coprescription of orlistat and sibutramine.

Rimonabant is a cannabinoid receptor antagonist which acts in the hypothalamus to reduce appetite and may also have beneficial effects in peripheral tissues. Its efficacy in patients with obesity and type 2 diabetes is similar to orlistat (see Box 5.29), including reducing HbA1c by ∼1%. However, rimonabant may exacerbate or induce depression and has been associated with a small increased risk of suicide, which has prevented it being licensed in the US and has limited its use in Europe. Drug therapy is usually reserved for patients with high risk of complications from obesity (see Fig. 5.12), and its optimum timing and duration are controversial.

Although life-long therapy is advocated for many drugs which reduce risk on the basis of relatively short-term research trials (e.g. drugs for hypertension and osteoporosis), patients who continue to take antiobesity drugs tend to regain weight with time (see Fig. 5.13). This, together with finite health-care resources, has led to the recommendation in some guidelines that anti-obesity drugs are used in the short term to maximise the weight loss achieved with low-calorie diets (so that inevitable regain of weight starts from a lower baseline), but are not used in the long-term maintenance of weight.