Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification: The COR-BMOD Trial

This 56-week, randomized, placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 +/- 4.2 kg/m(2)) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained-release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions. Co-primary end points were percentage change in weight and the proportion of participants who lost >= 5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with >= 1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 +/- 0.6% with placebo + BMOD vs. 9.3 +/- 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 +/- 0.9% (N = 106) vs. 11.5 +/- 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 +/- 0.6 vs. 7.8 +/- 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD-vs. placebo + BMOD-treated participants lost >= 5 and >= 10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.