Naltrexone-Bupropion ER for Weight Loss in Adults with Obesity

Efficacy and Recommendations

The American Gastroenterological Association (AGA) suggests using naltrexone-bupropion ER with lifestyle interventions compared to lifestyle interventions alone for weight management in adults with obesity or overweight with weight-related complications (conditional recommendation, moderate certainty evidence) 2
Naltrexone-bupropion ER produces modest weight loss of approximately 3.01% total body weight loss (TBWL) more than placebo (95% CI: 2.47-3.54% lower) 1
The combination of naltrexone-bupropion ER works by modulating central reward pathways triggered by food - bupropion inhibits reuptake of dopamine and norepinephrine while naltrexone antagonizes an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties 4

Naltrexone-bupropion ER may be particularly beneficial for patients who are attempting smoking cessation or have depression 2
Patients who describe food cravings or addictive behaviors related to food may respond well to this medication 4
Treatment discontinuation due to adverse effects is significantly higher with naltrexone-bupropion ER compared to placebo (25% vs 10%; RR 2.39; 95% CI 1.69-3.37) 2, 3
Most common adverse effects include nausea, vomiting, headache, dizziness, and depression 2
Blood pressure and heart rate should be monitored periodically, especially in the first 12 weeks of treatment 2

Naltrexone-bupropion ER produces less weight loss compared to other FDA-approved weight loss medications, such as semaglutide 2.4 mg, liraglutide 3.0 mg, and phentermine-topiramate ER 1
Concerns about cardiovascular safety as cardiovascular outcome trials were terminated early 5

Consider naltrexone-bupropion ER for patients with obesity or overweight with weight-related complications who also have depression or are attempting smoking cessation 2, 5
Ensure patients are also following lifestyle interventions including hypocaloric diet and increased physical activity 2, 3
Monitor for adverse effects, particularly in the first few weeks of treatment, and evaluate efficacy at 12 weeks 2, 6