Novel cannabinoid receptor 1 inverse agonist a promising medication for obesity

Treatment with the novel cannabinoid receptor 1 (CB1R) inverse agonist monlunabant appears to yield significant and clinically meaningful weight loss in adults with obesity and metabolic syndrome, according to a phase IIa trial.

A total of 243 participants, enrolled across 25 outpatient research centres in Canada, were randomly assigned to receive once-daily oral tablets of monlunabant at 10 mg (n=61), 20 mg (n=61), 50 mg (n=60), or placebo (n=61) for 16 weeks. The primary endpoint was mean bodyweight change from baseline. Safety was also evaluated.

Of the participants, 242 (69 percent female) received treatment and 183 completed the trial (82 percent in the monlunabant 10-mg arm, 70 percent in the 20-mg arm, 57 percent in the 50-mg arm, and 93 percent in the placebo arm).

At week 16, monlunabant was associated with significant weight loss compared with placebo, with least squares mean difference of –6.4 kg in the 10-mg arm, –6.9 kg in the 20-mg arm, and –8.0 kg in the 50-mg arm.

In terms of safety, mild-to-moderate gastrointestinal adverse events and psychiatric disorders were documented in 69 percent of participants in the monlunabant 10-mg arm, 78 percent in the 20-mg arm, 92 percent in the 50-mg arm, and 69 percent in the placebo arm. Treatment discontinuation due to adverse events appeared dose-dependent, occurring in 13 percent, 27 percent, 42 percent, and 0 percent in the respective treatment arms. The most common AEs were nausea, anxiety, diarrhoea, irritability, and sleep disorder. None of the participants died during the trial.