A randomized trial of lifestyle modification and taranabant for maintaining weight loss achieved with a low-calorie diet

Abstract

Improving the maintenance of weight loss remains a critical challenge for obesity researchers. The present 1-year, randomized, placebo-controlled trial evaluated the safety and efficacy of weight maintenance counseling combined with either placebo or the cannabinoid-1 receptor inverse agonist, taranabant, for sustaining prior weight loss achieved on a low-calorie diet (LCD). Seven hundred eighty-four individuals who had lost ≥ 6% of body weight during six initial weeks of treatment with an 800 kcal/day liquid LCD were randomly assigned to placebo or once-daily taranabant in doses of 0.5, 1, or 2 mg. All participants were provided monthly, on-site behavioral weight maintenance counseling, as well as monthly phone calls. The primary end point was change in body weight from randomization to week 52. The randomized participants lost an average of 9.6 kg (9.5% of initial weight) during the 6-week LCD. The model-adjusted mean change in body weight during the subsequent 1 year was +1.7 kg for placebo, compared with -0.1, -0.6, and -1.2 kg for the taranabant 0.5, 1, and 2 mg doses, respectively (all P values ≤ 0.007 vs. placebo). The incidences of psychiatric-related adverse events, including irritability, were higher for taranabant 1 and 2 mg vs. placebo (P ≤ 0.038). In addition to reporting data on the safety and efficacy of taranabant, this study provides a method for studying the combination of lifestyle modification and pharmacotherapy for weight maintenance after diet-induced weight loss.

Figures

Figure 1

CONSORT diagram illustrating participant flow through study.

Figure 2A

Percentage of participants who maintained ≥ 5% weight loss (as measured from week -14, start of low-calorie diet program) at post-randomization weeks 24 and 52 (N = 137). Note.Individuals who missed the assessment were assumed not to have maintained the loss.

Figure 2B

Percentage of participants who maintained ≥ 10% weight loss (as measured from week -14, start of low-calorie diet program) at post-randomization weeks 24 and 52 (N = 137). Note.Individuals who missed the assessment were assumed not to have maintained the loss.

Figure 2C

Mean percentage change in body weight from week -14 [start of low-calorie diet (LCD) program] to week 52. Note. Data for body weight are observed means ± SE for individuals available at each scheduled visit. Values at week -14 (screening) were set to 0.