The cornerstones of treatment for obesity, and even more so for simple overweight, are dietary measures and physical exercise. There are no drugs with a favourable harm-benefit balance in this setting. A fixed-dose combination of topiramate, an antiepileptic drug, and phentermine, an appetite-suppressant amphetamine, has been refused marketing authorisation in the European Union, after being licensed in the United States. There are no randomised controlled trials of topiramate + phentermine in the prevention of complications of obesity. In the three available placebo-controlled trials, patients treated with topiramate 46 mg per day + phentermine 7.5 mg per day for between 1 and 2 years lost about 6-8 kg more than patients who received a placebo. About one-quarter of this weight loss was regained within a year after treatment discontinuation. The known adverse effects of the two drugs composing this combination are additive, and include psychiatric disorders, cardiac arrhythmias and metabolic acidosis. The risk of serious cardiovascular disorders was not adequately studied during clinical trials. Many women of child-bearing age would be exposed to this combination, which can provoke fetal abnormalities, including cleft palate, if taken during pregnancy. In practice, the topiramate + phentermine combination has an unfavourable harm-benefit balance and has no place in the treatment of obesity.