Apovian 2013 (COR-II): naltrexone-bupropion for weight loss

What they tested

1,496 adults were randomly assigned, 2 to 1, to sustained-release naltrexone 32 mg a day plus sustained-release bupropion 360 mg a day, or to placebo, for up to 56 weeks. Neither patients nor staff knew who got which.

The main measures were the percentage of weight lost and the share of people who lost at least 5% of their weight at week 28. The trial was part of the CONTRAVE Obesity Research program.

What they found

At week 28, weight change was -6.5% on naltrexone-bupropion and -1.9% on placebo. At week 56 it was -6.4% and -1.2%.

More people on the drug lost at least 5% of their weight: 55.6% against 17.5% at week 28, and 50.5% against 17.1% at week 56.

The drug also led to bigger improvements in several heart and metabolic risk markers, in weight-related quality of life and in people's sense of control over eating.

Nausea was the most common side effect. It was generally mild to moderate and passed with time. Depression and suicidality were not more common than on placebo.

Limits

• The abstract doesn't say how many people finished the trial or how people who dropped out were counted.
• It enrolled adults with obesity or overweight plus risk factors, not people being treated for drinking, so it says nothing about alcohol.
• The naltrexone in this combination is a 32 mg sustained-release form, different from the 50 mg tablets used for alcohol.

What it means if you're considering naltrexone

This trial is about the weight-loss combination sold as Contrave, not about naltrexone on its own. It found the combination led to more weight loss than placebo over 56 weeks, with nausea as the main trade-off. The site's guide to naltrexone and bupropion notes that COR-II is not one of the trials in the Contrave label's results table.