Key Research Findings

Naltrexone/bupropion is an investigational combination medication for weight loss and maintenance in individuals who are obese or have a BMI of 27 kg/m² or higher with co-existing conditions such as diabetes, hypertension, or high cholesterol. 10 Combined results from four phase 3 trials demonstrated a significant weight loss of 4.7% (ranging from 3.2% to 5.2%) with naltrexone/bupropion compared to placebo after one year (p < 0.001 versus placebo in each trial). 10 Moreover, a greater proportion of patients achieved at least 5% weight loss with naltrexone/bupropion, ranging from 26% to 33% (p < 0.001 versus placebo in each trial). 10 The majority of phase 3 trials also revealed improvements in the proportion of patients reaching a 10% weight loss milestone, waist circumference, triglyceride levels, high-density lipoprotein (HDL) cholesterol, fasting insulin levels, insulin resistance, and obesity-related quality of life with naltrexone/bupropion compared to placebo. 10 In individuals with diabetes, naltrexone/bupropion therapy resulted in a decrease in hemoglobin A1c (HbA1c) by approximately 0.5% more than placebo (p < 0.001). 10

Reasons for Side Effects

Side effects associated with naltrexone/bupropion are likely due to the mechanisms of action of both naltrexone and bupropion. 8 Naltrexone is an opioid antagonist, while bupropion is a noradrenergic/dopaminergic antidepressant. 8 These medications influence the reward system in the brain, potentially affecting eating behavior through their impact on food reward. 8 Additionally, these medications can impact various systems in the body, including the digestive, nervous, and cardiovascular systems. 8

Common Side Effects

Nausea

A common side effect reported with naltrexone/bupropion is nausea. 10

Constipation

Constipation is another common side effect associated with naltrexone/bupropion. 10

Vomiting

Vomiting has been reported as a common side effect of naltrexone/bupropion. 10

Dizziness

Dizziness is a common side effect associated with naltrexone/bupropion. 10

Dry Mouth

Dry mouth is a common side effect reported with naltrexone/bupropion. 10

Side Effect Management

Nausea

Nausea can sometimes be alleviated by eating smaller, more frequent meals. 10 Anti-nausea medications can also be prescribed by a healthcare professional. 10

Constipation

Constipation may be managed by ensuring adequate fluid intake and consuming a diet rich in fiber. 10 Laxatives can also be prescribed by a healthcare professional. 10

Vomiting

Vomiting may be reduced by eating smaller, more frequent meals. 10 Anti-emetics can be prescribed by a healthcare professional to help manage vomiting. 10

Dizziness

Dizziness can sometimes be lessened by rising slowly from a seated or lying position and maintaining adequate hydration. 10 Anti-vertigo medications can also be prescribed by a healthcare professional. 10

Dry Mouth

Dry mouth can be addressed by staying hydrated. 10 Medications to alleviate dry mouth can also be prescribed by a healthcare professional. 10

Research Comparisons

Similarities in Research

Multiple studies have demonstrated the efficacy of naltrexone/bupropion in inducing weight loss compared to placebo. 10 , 8 These studies also indicate that naltrexone/bupropion can improve obesity-related complications. 10 , 8

Differences in Research

Findings regarding the safety of naltrexone/bupropion vary across studies. 10 , 3 One study 10 observed less improvement in systolic blood pressure and pulse rate with naltrexone/bupropion compared to placebo, prompting concerns regarding its potential impact on cardiovascular health. 3 highlighted the need for further research to determine the cardiovascular safety of naltrexone/bupropion. 10

Considerations for Real-World Application

While naltrexone/bupropion shows promise in weight management, it is crucial to recognize the potential side effects associated with its use. 10 , 8 Therefore, individuals considering this medication should consult with a healthcare professional to discuss their specific situation and choose an appropriate treatment plan. 8

Limitations of Current Research

The long-term safety and efficacy of naltrexone/bupropion remain to be fully established. 10 Further research is also required to investigate its potential impact on cardiovascular health. 3

Future Research Directions

Future research should focus on evaluating the long-term safety and efficacy of naltrexone/bupropion, exploring its cardiovascular effects, and developing new treatment approaches to minimize side effects. 10 , 3

Conclusion

Naltrexone/bupropion presents a promising avenue for weight management; however, it is important to be aware of its associated side effects. 10 , 8 Individuals considering this medication should consult with a healthcare professional to discuss their individual circumstances and select a suitable treatment plan. 8