Greenway 2009: naltrexone plus bupropion vs each drug alone for obesity

What they tested

Participants were randomly assigned for 24 weeks to bupropion alone (400 mg a day, sustained-release), naltrexone alone (48 mg a day, immediate-release), a placebo (dummy pill), or bupropion 400 mg plus naltrexone at 16, 32 or 48 mg a day. Neither participants nor staff knew who had which. There was also a 24-week extension.

Everyone had a minimal diet and exercise program. The main measure was percentage weight change at week 24 in everyone randomized, comparing the 48 mg combination with placebo and with each drug alone.

What they found

Compared with placebo, weight loss at 24 weeks was 4.62% greater with the 16 mg combination, 4.65% greater with 32 mg, and 3.53% greater with 48 mg (P < 0.001 for each).

All three combinations led to significantly more weight loss than either drug alone, except the 48 mg combination compared with bupropion alone.

Weight loss on the combinations continued after week 24. The authors said the 32 mg and 16 mg combinations showed more weight loss partly because fewer people dropped out of those groups.

The most common side effect was mild nausea that passed.

Limits

• The main results are at 24 weeks. The authors said further study was needed to show long-term effectiveness and safety.
• Participants had uncomplicated obesity, so the results may not apply to people with diabetes or other conditions.
• Dropout rates differed between groups and affected the results.

What it means if you're considering naltrexone

This was an early dose-finding trial of the naltrexone-bupropion pairing later sold as Contrave. It showed that the pair led to more weight loss than either drug on its own, with nausea as the main side effect.

It's about weight, not drinking. Naltrexone here was part of a combination at doses different from the 50 mg tablet used for alcohol.