OBJECTIVE: To examine the effects of naltrexone/bupropion (NB) combination 
therapy on weight and weight-related risk factors in overweight and obese 
participants.
DESIGN AND METHODS: CONTRAVE Obesity Research-II (COR-II) was a double-blind, 
placebo-controlled study of 1,496 obese (BMI 30-45 kg/m(2) ) or overweight 
(27-45 kg/m(2) with dyslipidemia and/or hypertension) participants randomized 
2:1 to combined naltrexone sustained-release (SR) (32 mg/day) plus bupropion SR 
(360 mg/day) (NB32) or placebo for up to 56 weeks. The co-primary endpoints were 
percent weight change and proportion achieving ≥ 5% weight loss at week 28.
RESULTS: Significantly (P < 0.001) greater weight loss was observed with NB32 
versus placebo at week 28 (-6.5% vs. -1.9%) and week 56 (-6.4% vs. -1.2%). More 
NB32-treated participants (P < 0.001) experienced ≥ 5% weight loss versus 
placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 
produced greater improvements in various cardiometabolic risk markers, 
participant-reported weight-related quality of life, and control of eating. The 
most common adverse event with NB was nausea, which was generally mild to 
moderate and transient. NB was not associated with increased events of 
depression or suicidality versus placebo.
CONCLUSION: NB represents a novel pharmacological approach to the treatment of 
obesity, and may become a valuable new therapeutic option.