Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.

Description

The effects of a new weight loss drug, tesofensine, an inhibitor of the presynaptic uptake of noradrenaline, dopamine, and serotonin, was evaluated in a phase II, randomized, double-blind, placebo-controlled trial. The study was conducted in five Danish obesity management centres. A sample of 203 obese patients (body mass index 30-40 kg/m2), mainly women, were randomized to receive placebo or tesofensine 0.25 mg, 0.5 mg, or 1.0 mg once daily. After the 24-week study follow-up, changes in body weight produced by tesofensine (-4.5%, -9.2%, and -10.6%, respectively, for 0.25 mg, 0.5 mg, and 1.0 mg) were greater (p<0.0001) than those observed with diet and placebo (-2.0%). Body fat, waist circumference, and sagittal diameter were decreased to a greater extent by tesofensine compared to diet and placebo. Tesofensine also improved plasma triglycerides, HbA1c, insulin, and adiponectin levels. The most common adverse events were dry mouth, nausea, constipation, hard stools, diarrhea, and insomnia. Tesofensine 1.0 mg produced a significant increase in systolic (6.8 mmHg) and diastolic (5.8 mmHg) blood pressure while heart rate was increased by 7.4 beats/min. in the tesofensine 0.5 mg arm. This study should pave the way to larger phase III efficacy and safety trials. An editorial by George A. Bray accompanied the article. He recognized that new weight loss agents are welcomed considering the obesity epidemic. He acknowledged that the study had several strengths such as a low dropout rate, a precise measurement of body fat by DEXA to confirm that weight loss was mainly fat, and improvements in quality of life with no substantial behavioural changes. However, as for other drugs, tesofensine generated some adverse events, particularly increases in blood pressure and heart rate. Therefore, phase III clinical trials are clearly warranted to further document the benefit/risk ratio of this new weight loss drug.