Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial

Authors: WADDEN, THOMAS - University Of Pennsylvania; FOREYT, JOHN - Children'S Nutrition Research Center (CNRC); FOSTER, GARY - Temple University; HILL, JAMES - University Of Colorado; KLEIN, SAMUEL - Washington University School Of Medicine; O'NEIL, PATRICK - Medical University Of South Carolina; PERRI, MICHAEL - University Of Florida; PI-SUNYER, F - St Luke'S-Roosevelt Hospital; ROCK, CHERYL - University Of California; ERICKSON, JANELLE - Incell Corporation; MAIER, HOLLY - Oregon Department Of Agriculture; DUNAYEVICH, EDUARDO - Oregon Department Of Agriculture

Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2010
Publication Date: 1/1/2011
Citation: Wadden, T.A., Foreyt, J.P., Foster, G.D., Hill, J.O., Klein, S., O'Neil, P.M., Perri, M.G., Pi-Sunyer, F.X., Rock, C.L., Erickson, J.S., Maier, H.N., Dunayevich, E. 2011. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 19:110-120.

Interpretive Summary: This study examined the safety and effectiveness of obtaining weight loss using a combination of the medications naltrexone and bupropion in conjunction with an intensive program of behavior modification. Inclusion of a strong behavioral program has been shown to increase weight loss compared to treatment by weight loss medication alone. Naltrexone is a drug that has been approved for the treatment of alcohol and opioid dependence. Bupropion is approved for depression and smoking cessation. Our studies demonstrated that these 2 drugs taken in combination with behavior modification (BMOD) are more effective for weight loss than behavior modification alone. The group demonstrated greater reductions in cardiovascular risk factors such as waist circumference and triglycerides. The current findings provide additional support for the effectiveness of combined naltrexone/bupropion therapy and suggest the further benefit of combining medication with a program of BMOD.

Technical Abstract: 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 greater than or equal to 5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with greater than or equal to 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 greater than or equal to 5 and greater than or equal to 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.