Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo

Frank L Greenway, Eduardo Dunayevich, Gary Tollefson, Janelle Erickson, Maria Guttadauria, Ken Fujioka, Michael Alexander Cowley

Research output: Contribution to journalArticleResearchpeer-review

158 Citations (Scopus)


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...
Original languageEnglish
Pages (from-to)4898 - 4906
Number of pages9
JournalThe Journal of Clinical Endocrinology and Metabolism
Issue number12
Publication statusPublished - 2009

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