Medicines for long-term obesity management

Drug therapy is part of the management of obesity. Clinical trials include diet and lifestyle interventions so patients still need to make lifestyle changes to  benefit from drug treatment. When to start drug treatment depends on the diet being used for the management of obesity. For example, drugs may not be needed in ketogenic diets because ketones suppress hunger. The selection of the first drug to try is informed by the presence of any contraindications. A history of epilepsy excludes bupropion/naltrexone, pancreatitis excludes liraglutide and semaglutide, cardiac arrhythmia excludes phentermine, and glaucoma, renal stone disease and planning a pregnancy would exclude topiramate. The second consideration is cost and there is also a need to consider which drug would be the safest to use long term.

Efficacy and safety

A dose that works well with no adverse effects for one individual could cause very severe and intolerable adverse effects in another. All prescribers should warn their patients about this, then, by mutual agreement, start one drug and be prepared to change to another if the first drug is not tolerated or is ineffective. Patients should be routinely monitored for adverse effects and the response to treatment.

Combination regimens

The body uses eight hormones to suppress hunger after a meal – cholecystokinin (CCK), peptide YY (PYY), glucagon-like peptide 1 (GLP-1), oxyntomodulin, uroguanilin, pancreatic polypetide, amylin and insulin. It therefore makes sense that several drugs may be needed in combination to control hunger. If each medicine is used at a low dose, some of the adverse effects may be avoided. However, there is currently no evidence to support this approach.

Phentermine has been combined with topiramate and is available as a single capsule in the USA. In Australia, the two drugs can be prescribed separately.8 Liraglutide or semaglutide could be combined with phentermine and topiramate or the bupropion/naltrexone combination. Phentermine should not be combined with bupropion/naltrexone. This is because bupropion has antidepressant effects and may increase cerebral serotonin. If that serotonin enters the blood stream, it normally would cause no harm, due to the avid uptake of serotonin by red blood cells. However, phentermine inhibits red cell uptake of serotonin so combining it with bupropion may increase circulating serotonin, which has been shown to cause heart valve fibrosis.

Treatment cost

Obesity rates are high in areas of low socioeconomic status. It is therefore important to consider the cost of the treatment when selecting a drug, a combination of drugs and the doses to be used. There is no subsidy for drugs that are approved for weight loss in Australia.

Duration of therapy

The hormone changes leading to increased hunger are very long lasting (at least six years, so probably life-long).5 This should be taken into account when considering which drug should be chosen, in addition to dietary therapy, for the maintenance phase of weight loss.


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