Naltrexone and metformin are two medicines that might help with weight loss. Naltrexone is usually used to treat addiction, but it can also affect how our brains control hunger and metabolism. Metformin helps people with diabetes manage their blood sugar levels, and some people have found it helps them lose weight too.
When you take both medicines together, they work on different parts of the body that help us regulate our weight.
This could be a more effective way to lose weight for people who are struggling with obesity. It might also help reduce cravings for overeating and improve overall health. For those who haven’t had success with dieting or exercise alone, this combination therapy could be a helpful tool in their journey to manage their weight.
Naltrexone works by blocking opioid receptors in the brain, which are involved in the regulation of appetite and food intake. By inhibiting these receptors, naltrexone reduces the pleasure and reward associated with eating, particularly the consumption of high-calorie, palatable foods. This leads to a decrease in overall food intake and helps in weight loss.
Metformin influences weight loss through several mechanisms.
It activates an enzyme called AMP-activated protein kinase (AMPK) in the liver and skeletal muscles, which enhances the uptake of glucose and reduces gluconeogenesis (the production of glucose from non-carbohydrate sources). This helps lower insulin levels and improves insulin sensitivity. Additionally, metformin alters the gut microbiome, leading to changes in the production of short-chain fatty acids and other metabolites that can influence energy balance and fat storage.
Metformin also increases the levels of the peptide hormone GDF15, which suppresses appetite and contributes to weight loss.
Naltrexone and Metformin for Weight Loss: Clinical Studies and Trials
Systematic Review (2020): A systematic review analyzed 10 randomized controlled trials and 3 non-randomized studies on naltrexone/bupropion for weight loss. The review found that naltrexone/bupropion treatment resulted in a mean weight loss of 5-10% in overweight subjects. The treatment was well-tolerated, with side effects being manageable.
Safety and Efficacy Study (2021): This study assessed the safety and efficacy of naltrexone/bupropion in adult patients.
The primary outcome was weight loss of at least 5% or 10%. The study concluded that naltrexone/bupropion is effective for weight loss and is generally safe.
Meta-Analysis (2020): A meta-analysis of 21 trials (n=1004) showed that metformin treatment resulted in a modest reduction in BMI (weighted mean difference -0.98). The most significant reduction was observed in patients with a BMI >35 kg/m² (WMD -1.12).
However, the reduction was not sufficient to meet the criteria for a weight loss drug (5% of baseline body weight).
Obesity Treatment Study (2020): This study focused on the effects of metformin in different populations. It found that metformin led to a one-unit reduction in BMI at the end of treatment. The reduction was most significant in patients with simple obesity.
Contrave (Naltrexone/Bupropion) Study (2015): The combination of naltrexone and bupropion, marketed as Contrave, was found to produce clinically significant weight loss when combined with a diet and exercise program.
It was particularly effective in patients with diabetes.
These studies highlight the potential of naltrexone and metformin for weight loss, though their efficacy varies across different populations and treatment durations.
Starting Dose:
Week 1: 1 tablet (8 mg naltrexone / 90 mg bupropion) orally once a day in the morning.
Week 2: 1 tablet orally twice a day (morning and evening).
Week 3: 2 tablets orally in the morning and 1 tablet orally in the evening.
Week 4: 2 tablets orally twice a day (morning and evening).
Maintenance Dose:
2 tablets orally twice a day (morning and evening).
Maximum Dose:
4 tablets/day (32 mg naltrexone / 360 mg bupropion).
Considerations:
Therapy should be discontinued if a patient has not lost at least 5% of baseline body weight after 12 weeks at maintenance dose.
Renal and hepatic impairments require dose adjustments.
Concomitant use with MAOIs is contraindicated.
Starting Dose:
Adults: 500 mg orally twice per day with meals or 850 mg orally once per day with an evening meal.
Adjustments:
Dosage is tailored based on individual health factors under the guidance of a healthcare professional.
If well-tolerated, the dose may be gradually increased.
Maximum Dose:
2,550 mg per day.
Considerations:
Metformin should be taken with meals to reduce gastrointestinal side effects.
Regular monitoring of renal function is recommended.
Combining metformin with lifestyle changes such as diet and exercise is recommended for optimal weight loss.
Nausea
Vomiting
Loss of appetite
Joint pain
Muscle cramps
Headache
Dizziness
Drowsiness
Sleep problems (insomnia)
Tooth pain or cold symptoms (stuffy nose, sneezing, sore throat)
Anxiety or nervousness
Anxiety, irritability, or nervousness
Changes in energy levels (high energy or fatigue)
Chills
Increased thirst
Sexual side effects (delayed ejaculation or erectile dysfunction)
Skin rash
Liver problems (hepatitis)
Mental health changes (depression, suicidal thoughts)
Risk of opioid withdrawal if an opioid is taken within 10 days of starting naltrexone
Risk of opioid overdose if an opioid is taken during naltrexone treatment
Nausea
Vomiting
Diarrhea
Stomach pain or discomfort
Bloating
Gas
Constipation
Weight loss
Headache
Metallic taste in mouth
Heartburn
Indigestion
Excess air or gas in the stomach or intestines
Full feeling
Lower back or side pain
Muscle pain or cramping
Painful or difficult urination
Sleepiness
Lactic acidosis (build-up of lactic acid in the blood)
Hypoglycemia (low blood sugar)
Severe skin reactions (rash, itching, swelling, redness)
Severe allergic reactions (difficulty breathing, swelling of the face, lips, or tongue)
Monitoring and managing side effects is crucial to ensure patient safety and treatment efficacy. Regular follow-ups with healthcare providers, adherence to prescribed dosages, and reporting any unusual symptoms promptly can help mitigate risks. Adjustments to the treatment plan may be necessary based on individual responses to the medications.
Naltrexone and Metformin Therapy for Weight Loss: Eligibility Criteria, Contraindications, and Beneficial Patient Populations
Body Mass Index (BMI): Patients with a BMI of 30 kg/m² or greater, or 27 kg/m² or greater with associated comorbidities such as hypertension, diabetes, or dyslipidemia.
Comprehensive Lifestyle Intervention: Patients must be engaged in a comprehensive lifestyle intervention program that includes dietary changes, physical activity, and behavioral modifications.
Previous Weight Loss Attempts: Patients who have attempted weight loss through lifestyle interventions without achieving desired results may be considered.
Naltrexone:
Current use of opioid medications or history of opioid dependence.
Acute hepatitis or hepatic failure.
Allergy or hypersensitivity to naltrexone or any of its components.
Recent use of opioids or positive urine screen for opioids.
Metformin:
Severe renal impairment or end-stage renal disease.
Known hypersensitivity to metformin or any of its components.
Diabetic ketoacidosis.
Metformin-associated lactic acidosis (MALA) history.
Patients with Obesity and Type 2 Diabetes: Metformin has shown weight loss benefits in patients with obesity and type 2 diabetes.
Patients with Prediabetes: Metformin is effective in preventing the progression to type 2 diabetes in patients with prediabetes.
Patients with Alcohol Use Disorder: Naltrexone can be beneficial for weight loss in patients with alcohol use disorder as it helps reduce cravings and consumption of alcohol.
Patients with a History of Failed Weight Loss Attempts: Both naltrexone and metformin can be considered for patients who have not achieved weight loss through lifestyle interventions alone.
Naltrexone and metformin have shown promise in aiding weight loss, particularly in patients with obesity and type 2 diabetes. The combination of these medications can lead to significant weight reduction and improved metabolic health.
However, it is essential to note that individual results may vary, and further research is needed to fully understand their efficacy and potential side effects.
The eligibility criteria for this treatment include a body mass index (BMI) of 30 kg/m² or greater, or 27 kg/m² or greater with associated comorbidities. Patients must also be engaged in a comprehensive lifestyle intervention program that includes dietary changes, physical activity, and behavioral modifications.
Common side effects of naltrexone and metformin include:
Severe side effects can include:
Monitoring and managing side effects is crucial to ensure patient safety and treatment efficacy. Regular follow-ups with healthcare providers, adherence to prescribed dosages, and reporting any unusual symptoms promptly are essential.
Naltrexone and metformin can be beneficial for patients with obesity and type 2 diabetes, prediabetes, alcohol use disorder, or a history of failed weight loss attempts. However, it is crucial to consult with a healthcare provider before starting this treatment, as they will assess individual eligibility and provide personalized guidance on the potential benefits and risks.