GENEVA — Overweight and obese patients achieved significant weight loss and improved metabolic parameters using taranabant, according to interim results from a 2-year study.
Taranabant is a structurally distinct, highly selective cannabinoid-1 (CB-1) receptor inverse agonist under investigation for the treatment of obesity.
“With diet and exercise, treatment with taranabant 2 mg for 52 weeks was generally well tolerated and led to clinically meaningful weight loss in obese and overweight patients,” said Dr. Joe Proietto of the University of Melbourne, who presented the results at the 16th European Congress on Obesity. “Relative to taranabant dosed at 2 mg, the 4-mg and 6-mg doses were associated with slightly more weight loss, but at an increased incidence of adverse events.”
In a previous phase II study with taranabant dosed at 0.5, 2, 4, or 6 mg/day, a dose-dependent and clinically meaningful weight loss was seen in obese patients at 12 weeks, compared with placebo. This current ongoing 2-year phase III study was designed to evaluate the long-term efficacy and safety taranabant in overweight and obese patients. End points included changes in body weight, waist circumference, and serum lipids, and the proportion of subjects with metabolic syndrome.
After a 2-week single-blind placebo and diet run-in period, 2,502 overweight (body mass index greater than 25 kg/m
The researchers found that the least-squares mean changes from baseline in body weight were −2.6 kg, −6.6 kg, and −8.1 kg in patients receiving placebo, taranabant 2 mg, and taranabant 4 mg, respectively.
Compared with placebo, taranabant dosed at 2 and 4 mg showed significant improvement in waist circumference (−3.1%, −7.0%, and −7.5%, respectively) and a positive impact in changes in HDL cholesterol (7.0%, 13.2%, and 14.1%, respectively), triglycerides (4.0%, −3.1%, and −6.2%, respectively), and the proportion of patients with metabolic syndrome (47.3%, 36.0%, and 30.7%, respectively).
There were no significant changes seen in glucose metabolism—including fasting glucose, fasting insulin, or the quantitative insulin sensitivity check index measure of insulin sensitivity—or in blood pressure when compared with placebo.
After a year of diet and exercise, patients randomized to placebo showed a slight increase in triglycerides, for which Dr. Proietto had no conclusive explanation. Other studies also have shown slightly increased triglycerides, which tend to be fairly labile and can fluctuate in patients, according to Dr. Proietto.
Adverse events included gastrointestinal-related events in 28.5% of the placebo group and in 41.8% and 46.7% of the taranabant 2-mg and 4-mg groups, respectively. Psychiatric adverse events occurred in 20.4% of the placebo group and 28.3% and 40.2% of the taranabant 2-mg and 4-mg groups, respectively.
Dr. Proietto disclosed that he is a member of an advisory board for Merck & Co., which is developing taranabant. His institution participated in the current trial.
There was slightly more weight loss with higher doses of taranabant, but at an increased incidence of adverse events. DR. PROIETTO