Greenway 2010 (COR-I): naltrexone plus bupropion for weight loss

What they tested

Adults with a BMI of 30 to 45, or 27 to 45 with high blood lipids or high blood pressure, were randomly assigned to sustained-release naltrexone 32 mg plus bupropion 360 mg a day, naltrexone 16 mg plus bupropion 360 mg a day, or a matching placebo, for 56 weeks. Everyone was told to follow a mild calorie-cutting diet and exercise.

The two main measures were the percentage change in body weight and the share of people who lost 5% or more. The study was called Contrave Obesity Research I (COR-I).

What they found

Average weight change was -6.1% on the 32 mg combination, -5.0% on the 16 mg combination and -1.3% on placebo (p<0.0001 for each combination vs placebo).

A weight loss of 5% or more was reached by 48% on the 32 mg combination, 39% on the 16 mg combination, and 16% on placebo.

Of the 1,742 people randomized, 870 (50%) completed the 56 weeks, and 1,453 (83%) were included in the main analysis.

Nausea was the most frequent side effect: 29.8% on the 32 mg combination, 27.2% on 16 mg and 5.3% on placebo. Headache, constipation, dizziness, vomiting and dry mouth were also more common on the combination. Blood pressure rose by around 1.5 mm Hg at first, then fell to around 1 mm Hg below baseline. The combination was not linked to more depression or suicidality than placebo.

Limits

• Only half the participants completed the 56 weeks.
• The main analysis used each person's last weight while on the drug, which can make results look better than counting everyone who was randomized.
• It was funded by Orexigen Therapeutics, a drug company.

What it means if you're considering naltrexone

COR-I was a large phase 3 trial of the naltrexone-bupropion combination sold as Contrave. It showed more weight loss than placebo, with nausea as the most common problem.

It doesn't tell you about naltrexone for drinking. The doses and form of naltrexone here differ from the 50 mg tablet used for alcohol.