Combination of naltrexone plus bupropion could be used for obesity

January 01, 0001

Combination of naltrexone plus bupropion could be used for obesity

Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants. Men and women aged 18—65 years who had a body-mass index (BMI) of 30—45 kg/m2 and uncomplicated obesity or BMI 27—45 kg/m2 with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed- dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511).

Mean change in bodyweight was -1.3% in the placebo group, -6·1% in the naltrexone 32 mg plus bupropion group and -5·0% in the naltrexone 16 mg plus bupropion group (all significant vs placebo). 16% participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 48% assigned to naltrexone 32 mg plus bupropion (significant vs placebo) and 39% assigned to naltrexone 16 mg plus bupropion (significant vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 29.8% participants, naltrexone 16 mg plus bupropion 27.2%, placebo 5.3%). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo.

The researchers concluded: "A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity."

It would be interesting to know what happens to these study subjects long term, when continuing on active treatment or ceasing.

For the full abstract, click here.

The Lancet 376(9741):595-605, 21 August 2010 © 2010 Elsevier Limited
Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Frank L Greenway, Ken Fujioka, Raymond A Plodkowski et al for the COR-I Study Group. Correspondence to Prof Frank L Greenway: [email protected]

Category: T. Endocrine/Metabolic/Nutritional. Keywords: naltrexone, buproprion, weight los, overweight, obese, randomised, double-blind, placebo-controlled, phase 3 trial, journal watch.
Synopsis edited by Dr Stephen Wilkinson, Melbourne, Australia. Posted on Global Family Doctor 22 October 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.