Astrup A et al. (2008) Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 372: 1906–1913

Weight loss of 5–10% is associated with improved health in obese individuals; however, currently approved antiobesity drugs typically achieve <5 kg weight loss after 1 year. A double-blind, randomized, controlled, prospective trial by Astrup et al. has demonstrated that tesofensine effectively induces weight loss and improves quality of life in obese individuals.

All 203 participants were placed on an energy-restricted diet. After a 2-week run-in period, participants were randomly allocated to receive 0.25 mg, 0.5 mg or 1.0 mg tesofensine or placebo per day for 24 weeks. In the 161 patients who completed the study, significant, mean, placebo-adjusted weight losses of 4.7%, 9.2% and 10.4% were achieved in those receiving 0.25 mg, 0.5 mg or 1.0 mg of tesofensine, respectively. A similar outcome was achieved in the intention-to-treat population. The reduction in body weight was associated with a significant improvement in weight-related quality of life.

Although the weight loss achieved by the two highest doses was similar, the treatment-related adverse effects were more frequent with the 1.0 mg dose. The most common adverse effects associated with tesofensine were gastroenterological (dry mouth, nausea, constipation and diarrhea). Heart rate showed a dose-dependent increase in all three groups, up to 8.1 beats per minute.

The findings from this study suggest that 0.5 mg of tesofensine per day safely and effectively induces weight loss in obese patients. These promising findings now require validation and direct comparison with approved weight-loss drugs in large, phase III trials.