CONTEXT: The efficacy of current centrally acting obesity pharmacotherapies is limited by compensatory mechanisms that mitigate weight loss. OBJECTIVE: Our objective was to determine whether opioid receptor antagonism (naltrexone) plus pro-opiomelanocortin activation (bupropion) causes greater weight loss than placebo or monotherapy. DESIGN/ SETTING: A randomized, placebo- and monotherapy-controlled, double-blind, dose-finding trial was conducted from August 2005 to December 2006 in seven U.S. outpatient clinics. PARTICIPANTS: A total of 419 patients with uncomplicated obesity participated. INTERVENTIONS: Interventions included 24 wk of sustained-release bupropion (400 mg/d), immediate-release naltrexone (48 mg/d), placebo, and three combination therapy [naltrexone/bupropion (NB)] groups consisting of immediate-release naltrexone, 16, 32, or 48 mg/d, plus sustained-release bupropion (400 mg/d) with a 24-wk extension. A minimal diet and exercise component was also included. MAIN OUTCOME MEASURES: Percent weight change from baseline at wk 24 in the intent-to-treat population for NB48 vs. placebo and monotherapy was assessed. Other measurements included body mass index, waist circumference, fasting lipids, glycemic variables, safety, and tolerability. RESULTS: At wk 24, placebo-subtracted weight loss was -4.62% [95% confidence interval (CI) -6.24 to -2.99; P < 0.001] for NB16, -4.65% (95% CI -6.20 to -3.09; P < 0.001) for NB32, and -3.53% (95% CI -5.15 to -1.90; P < 0.001) for NB48. Weight loss was statistically significant vs. monotherapy for all three NB combinations with the exception of NB48 vs. bupropion. Weight loss with NB continued after wk 24. The most common treatment-emergent adverse event was mild transient nausea. CONCLUSIONS: NB caused gradual sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates. Further study is needed to demonstrate long-term efficacy and safety of NB.
RCT Entities:
CONTEXT: The efficacy of current centrally acting obesity pharmacotherapies is limited by compensatory mechanisms that mitigate weight loss. OBJECTIVE: Our objective was to determine whether opioid receptor antagonism (naltrexone) plus pro-opiomelanocortin activation (bupropion) causes greater weight loss than placebo or monotherapy. DESIGN/ SETTING: A randomized, placebo- and monotherapy-controlled, double-blind, dose-finding trial was conducted from August 2005 to December 2006 in seven U.S. outpatient clinics. PARTICIPANTS: A total of 419 patients with uncomplicated obesity participated. INTERVENTIONS: Interventions included 24 wk of sustained-release bupropion (400 mg/d), immediate-release naltrexone (48 mg/d), placebo, and three combination therapy [naltrexone/bupropion (NB)] groups consisting of immediate-release naltrexone, 16, 32, or 48 mg/d, plus sustained-release bupropion (400 mg/d) with a 24-wk extension. A minimal diet and exercise component was also included. MAIN OUTCOME MEASURES: Percent weight change from baseline at wk 24 in the intent-to-treat population for NB48 vs. placebo and monotherapy was assessed. Other measurements included body mass index, waist circumference, fasting lipids, glycemic variables, safety, and tolerability. RESULTS: At wk 24, placebo-subtracted weight loss was -4.62% [95% confidence interval (CI) -6.24 to -2.99; P < 0.001] for NB16, -4.65% (95% CI -6.20 to -3.09; P < 0.001) for NB32, and -3.53% (95% CI -5.15 to -1.90; P < 0.001) for NB48. Weight loss was statistically significant vs. monotherapy for all three NB combinations with the exception of NB48 vs. bupropion. Weight loss with NB continued after wk 24. The most common treatment-emergent adverse event was mild transient nausea. CONCLUSIONS: NB caused gradual sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates. Further study is needed to demonstrate long-term efficacy and safety of NB.