Tesofensine is a serotonin-noradrenaline-dopamine re-uptake inhibitor that was originally developed for the treatment of Parkinson’s and Alzheimer’s disease. Although development for these diseases has been discontinued, the discovery that tesofensine caused unintended weight loss in obese patients led to the initiation of new trials for the treatment of obesity. The drug works by suppressing hunger, leading to an energy deficit which burns off excess body fat. Neurosearch, the company that is developing tesofensine, has announced preliminary results from a phase II proof of concept study published online in the Oct 23 edition of the Lancet. The study, which was carried out in five centres in Denmark, involved 203 obese patients with body mass index of 30-40 kg/m2 and weighing just over 100kg at the start of the study. The patients ate a limited-energy diet and were assigned to tesofensine (0.25mg, 0.5mg or 1.0mg once daily) or placebo groups for 24 weeks. A total of 161 patients completed the study; mean weight loss for the placebo group was 2.2kg and for the tesofensine groups was 6.7 kg, 11.3 kg, and 12.8 kg (0.25mg, 0.5mg and 1.0mg respectively). For the 0.5 mg and 1.0 mg dose groups, the weight loss was around twice that achieved using sibutramine or rimonabant. The most common side-effects caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia; blood pressure was also increased in the 1.0 mg group.
The study authors conclude that the 0.5 mg dose of tesofensine is more promising than the 1.0 mg dose since it produces a similar weight loss with fewer side-effects, but say that larger phase III trials are needed to substantiate their findings.