Naltrexone/bupropion for weight loss: what the COR-II trial found

Why this study matters

Naltrexone/bupropion is one of the older prescription medicines for weight management. It combines two medicines that were first used for other conditions. COR-II was one of the large trials that tested whether the combination helps adults with a higher body weight lose weight, and how well people tolerate it. For a Canadian reader, this trial is part of the evidence base behind a medicine that is still in use, and it shows both what it can do and where its limits are.

Who was in the study

The trial enrolled 1,496 adults. They either had obesity, defined as a body mass index (BMI) of 30 to 45, or had overweight, defined as a BMI of 27 to 45, plus high cholesterol or high blood pressure. BMI is a number that compares weight with height. People with diabetes were excluded. The extracted data note that participants were mainly middle-aged White women. The trial ran for up to 56 weeks.

What the researchers did

This was a randomized, double-blind, placebo-controlled trial. Randomized means a computer decided by chance who got the medicine and who got placebo. Placebo is a dummy pill with no active medicine. Double-blind means neither the participants nor the study staff knew who was taking which.

People were assigned in a 2 to 1 ratio, so twice as many got the active medicine as placebo. The active treatment was naltrexone sustained-release 32 mg per day plus bupropion sustained-release 360 mg per day, a combination the study called NB32.

The two main outcomes, called co-primary endpoints, were measured at week 28: the percent change in body weight, and the proportion of people who lost at least 5% of their starting weight. Results at week 56 were also reported.

What they found

At week 28, mean weight change was -6.5% with naltrexone/bupropion and -1.9% with placebo (R32-C84). At week 56 it was -6.4% and -1.2%. The published summary we reviewed does not report the difference between groups with a confidence interval.

The abstract also reports that the medicine group had greater improvements in several heart and metabolic risk markers, in weight-related quality of life as reported by participants, and in control of eating. The summary does not give numbers for these.

The primary analysis used a method called "last observation carried forward". This means that if someone dropped out, their last recorded weight was used as if it were their final weight. This approach can make results look better than they would if everyone had been followed to the end (R32-C84).

Side effects and people who stopped

The most common side effect with naltrexone/bupropion was nausea, which the authors describe as generally mild to moderate and short-lived. The trial did not find more events of depression or suicidal thoughts with the medicine than with placebo.

Side effects led to stopping treatment in 24.3% of the medicine group and 13.8% of the placebo group. In each group, 54% of people completed treatment. The extracted data do not report an overall discontinuation percentage beyond this completion figure.

What this study does not tell you

• Nearly half of participants in each group did not complete treatment. High dropout makes any weight result less certain.
• The analysis carried forward the last on-treatment weight for people who left. The extracted data also note that at week 56 some participants were re-randomized, and their results were weighted differently, which makes the week 56 numbers harder to interpret.
• The participants were mainly middle-aged White women. Results may not apply to other groups.
• People with diabetes were excluded, so the trial says nothing about that group.
• The trial was 56 weeks long. It cannot say what happens over several years or after stopping.
• This trial cannot be compared directly with trials of other medicines, because the people, the lifestyle support, and the measurement methods differ.

What it means in Canada

This page describes one trial and does not say whether naltrexone/bupropion is right for anyone. To learn about the medicine itself, see naltrexone/bupropion in Canada. Information on what provincial plans pay for is at public drug coverage by province, and you can look at compare services to see how weight-management programs differ.

Related reading

Other studies in this library that bear on the same question.

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