Can a patient take naltrexone-bupropion and semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) together?

Concurrent Use of Naltrexone-Bupropion and Semaglutide for Weight Management

Yes, patients can take naltrexone-bupropion and semaglutide together for weight management, as there are no documented contraindications between these medications. While there are no specific studies examining this combination, their different mechanisms of action may provide complementary benefits for weight loss.

Mechanisms of Action

• Naltrexone-bupropion (Contrave/Mysimba) works through:

  • Bupropion: Dopamine and norepinephrine reuptake inhibitor that modulates central reward pathways triggered by food 1
  • Naltrexone: Opioid antagonist that blocks inhibitory feedback on bupropion's anorectic properties 1
  • Together they activate pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus 1

• Semaglutide (Wegovy) works through:

  • GLP-1 receptor agonism affecting appetite centers in the hypothalamus 1
  • Delayed gastric emptying 1
  • Increased satiety and reduced food intake 1

Efficacy Comparison

• Semaglutide demonstrates superior weight loss efficacy:

  • Average weight loss of 9.6% from baseline 1
  • Greater weight reduction than naltrexone-bupropion (10.76% vs 3.01% compared to placebo) 1, 2

• Naltrexone-bupropion provides modest weight loss:

  • Average weight loss of 5.0% from baseline 1
  • Approximately 3% greater weight loss than placebo 1

Side Effect Considerations

Naltrexone-Bupropion Side Effects:

• Common: Nausea, constipation, headache, dizziness, insomnia, dry mouth 1
• Cardiovascular: May increase blood pressure (RR 1.72) 1, 2
• Neuropsychiatric: Risk of seizures, cognitive impairment, anxiety, sleep disorders 3
• Black box warning: Risk of suicidal behavior/ideation in people younger than 24 years with depression 1

Semaglutide Side Effects:

• Common: Gastrointestinal effects (nausea, vomiting, diarrhea, esophageal reflux) 1
• May cause cholelithiasis and gallstone-related complications 1
• Potential risk of pancreatitis 1
• Black box warning: Risk of thyroid C-cell tumors in rodents (human relevance not determined) 1

Important Monitoring Considerations

• Blood pressure should be monitored closely as:

  • Naltrexone-bupropion can increase blood pressure 1
  • Semaglutide generally has beneficial effects on blood pressure 2

• Renal function:

  • Use caution with semaglutide in patients with kidney disease when initiating or increasing doses 1
  • For naltrexone-bupropion, reduce dose in moderate to severe renal impairment 1

• Gastrointestinal symptoms:

  • Both medications can cause GI side effects, potentially additive 1
  • Consider slower titration of both medications if GI symptoms occur 1

Special Considerations

• Opioid use:

  • Naltrexone component blocks opioid receptors and should be discontinued before procedures requiring opioid analgesia 1
  • Consider holding naltrexone-bupropion before endoscopic procedures where fentanyl might be used 1

• Seizure risk:

  • Avoid naltrexone-bupropion in patients with seizure disorders 1
  • Use caution in patients with factors that lower seizure threshold 1

• Diabetes management:

  • Semaglutide has beneficial effects on glycemic control 1, 2
  • Monitor for hypoglycemia in patients with diabetes on insulin or sulfonylureas 1

Practical Approach to Combination Therapy

1. Consider starting with semaglutide alone given its superior efficacy profile 1, 2
2. If weight loss is inadequate with semaglutide alone, consider adding naltrexone-bupropion
3. When using both medications:
   • Follow standard titration schedules for each medication
   • For semaglutide: Start at 0.25mg weekly, increasing by 0.25mg every 4 weeks to target dose of 2.4mg 1
   • For naltrexone-bupropion: Start with 1 tablet daily, increasing weekly to target dose of 2 tablets twice daily 1
   • Monitor for overlapping side effects, particularly GI symptoms 1

Conclusion

While combining these medications is not explicitly contraindicated, patients should be closely monitored for potential additive side effects, particularly gastrointestinal symptoms and blood pressure changes. The superior efficacy profile of semaglutide may make it the preferred first-line agent, with naltrexone-bupropion added if additional weight loss is needed.