Contrave vs Zepbound: Which weight loss solution is right for you?

Obesity is a complex chronic disease that affects more than 40% of the U.S. adult population. There are medical treatment options available, including anti-obesity medications (AOMs), that can help patients lose weight and improve their overall health. Two FDA-approved medications that you may consider on your weight loss journey are Zepbound® and Contrave®. While both Zepbound and Contrave aid in weight loss, understanding their differences can help patients and medical clinicians make informed decisions and develop effective treatment plans. In this article, we will discuss the similarities and differences between Contrave and Zepbound, why one medication may be chosen over another, and how much weight loss patients who take these medications can expect.

Contrave vs. Zepbound? Get the facts to make your decision

Overview of Contrave

Contrave is a combination medication of naltrexone and bupropion and is FDA-approved for weight loss in individuals with a BMI of 30+, or 27+ with one or more weight-related comorbidities in combination with a low-calorie eating pattern and increased physical activity. Naltrexone is an opioid antagonist medication while bupropion is an antidepressant medication. Together, these medications act on the reward center in the brain to reduce food cravings, reduce appetite, and promote weight loss. In clinical trials, participants taking the maximum daily dose of Contrave for weight loss (32 mg naltrexone/360 mg bupropion) in combination with healthy lifestyle changes lost an average of 8.1% of their total body weight over 56 weeks. Contrave’s dual-action mechanism targeting both food cravings and appetite makes it a promising option for those looking to achieve and maintain a healthy weight. Additionally, its lower cost  may make it a more affordable choice for individuals living with obesity.

Overview of Zepbound

Zepbound contains the active ingredient tirzepatide, a dual GLP-1/GIP agonist.  By activating GLP-1 receptors, Zepbound acts on the brain to diminish appetite and cravings and on the stomach to slow down digestion. The GIP receptor activity is believed to further promote weight loss, partially due to its impacts on lipid and glucose metabolism. Zepbound is FDA-approved for weight loss in patients with obesity or overweight with at least one weight-related comorbidity in combination with a low-calorie eating pattern and increased physical activity.  It has also been FDA-approved for moderate-to-severe obstructive sleep apnea in individuals with obesity. Mounjaro, which also contains tirzepatide, is FDA-approved for the treatment of type 2 diabetes. 

Clinical trials, such as the SURMOUNT-1 trial, have demonstrated Zepbound's effectiveness in helping patients achieve significant weight loss. In this particular trial, participants taking the highest dose of Zepbound (15 mg) experienced an average total body weight loss of 22.5% at approximately one year. Even those on a lower maintenance dose (5 mg) achieved a significant average total body weight loss of 16%. 
Zepbound vs. Contrave

While both Contrave and Zepbound are FDA-approved for weight loss, there are significant differences between the two.  As described above, they act on the body in different ways to promote weight loss and a decrease in appetite and cravings. Before deciding which medication is right for you, it's important to have a discussion with your healthcare provider. They will consider your medical history, current medications, lifestyle factors, and individual needs to help determine the most appropriate option for you.

Different forms of dosage

Zepbound is an injectable medication while Contrave is in pill form. Both Zepbound and Contrave require dose titration which means slowly increasing your dose when starting the medication. However, the cadence and schedule should be determined based on your response to the medication by a healthcare provider who can closely monitor symptoms and make adjustments as needed.

Contrave dosing

Contrave is available in pill form and is recommended to be taken with meals to help reduce side effects. Each tablet contains 8 mg of naltrexone and 90 mg of bupropion. Dosing typically starts with one pill daily in the first week and gradually increases until reaching the full dose of two tablets twice daily by week four.

A typical Contrave dosing schedule is as follows:

• Week 1: 1 pill daily
• Week 2: 1 pill twice daily (morning and evening)
• Week 3: 2 pills in the morning, 1 pill in the evening
• Week 4 and beyond: 2 pills twice daily (morning and evening)

Zepbound dosing

Zepbound is available as a once-weekly, single-use injectable pen in six different doses, starting at 2.5 mg and increasing in 2.5 mg increments to a maximum dose of 15 mg. The pens are designed to deliver one entire dose (e.g., 5 mg rather than two doses of 2.5 mg). Zepbound is also available in single-dose vials of 2.5, 5, 7.5 and 10 mg doses.

Typically, the medication dose is increased every four weeks, as long as it is tolerated and safe to do so. Some patients stay at lower doses rather than increase to the full 15 mg dose, depending on how they are responding to the medication. Ideally, a prescriber will work closely with each patient to determine the appropriate titration and dosing schedule for each individual.

Contrave vs Zepbound weight loss results

Weight loss results from Contrave and Zepbound will vary from person to person as weight loss is influenced by numerous factors including nutrition, physical activity, environment, medical history, and other medications you may be prescribed.

Contrave weight loss results

In clinical trials, participants who took the maximum dose of Contrave for weight loss (two tablets twice daily, totaling 32 mg of naltrexone and 360 mg of bupropion per day) along with healthy lifestyle changes lost an average of 8.1% of their total body weight over 56 weeks, compared to 4.9% in those who received a placebo plus healthy lifestyle intervention.

Zepbound weight loss results 

In clinical trials, Zepbound has shown the most significant weight loss results of any FDA-approved weight loss medication to date. At the maximum dose (15 mg weekly), patients lost an average of 22.5–26% of their total body weight, based on the SURMOUNT-1 and  SURMOUNT-3 trials.  Furthermore, clinical studies have shown taking the  5 mg dose, along with a reduced-calorie diet and increased physical activity, led to an averageof ~15% body weight loss over 72 weeks.

Side effects

All medications carry some risk of side effects and before starting medications you prescriber should review these with you. Once you begin treatment, monitor your symptoms closely and keep your clinician informed.

Side effects of Contrave

Contrave is started at a low dose and increased slowly to build tolerance and minimize the risk of side effects. The most common side effects of Contrave include:

• Nausea
• Constipation
• Headache
• Vomiting
• Fatigue
• Dizziness
• Trouble sleeping
• Dry mouth

Contrave can cause an increase in blood pressure, so blood pressure should be monitored closely while on Contrave, especially if a patient has a history of high blood pressure. Mood should also be monitored closely while on Contrave as this medication may cause mood disturbances.

Patients taking Contrave should notify their healthcare provider right away should they experience any side effects from the medication.  Additionally, Contrave cannot be taken with opiate pain medications. 

Side effects of Zepbound

Zepbound is started at a low dose and increased slowly to build tolerance and minimize the risk of side effects. The most common side effects for Zepbound include:

• Heartburn
• Nausea
• Vomiting
• Constipation
• Diarrhea
• Abdominal discomfort
• Fatigue

Gallbladder disease and pancreatitis are other potential side effects  While on this medication it is important to be able to get in touch with your clinician should you have significant side effects and to regularly monitor your progress on the medication.

Eligibility for Contrave vs Zepbound

Zepbound and Contrave are both FDA-approved for treating adults with obesity or with overweight and at least one weight-related medical condition, such as:

• Type 2 diabetes
• High blood pressure
• High cholesterol

In addition, Zepbound is approved for moderate-to-severe obstructive sleep apnea in adults with obesity. 

Please note that even if you have obesity or overweight, depending on your medical history and other medications you are taking, Zepbound and/or Contrave may not be safe choices. Lack of insurance coverage can also be a barrier to using these medications; however, there are savings programs that may help bring down the cost to a more affordable range.

Contrave and Zepbound insurance coverage

The cost of Zepbound and Contrave will depend on your insurance benefits and the specifics of your individual plan. Each plan will have a list of covered medications (the “formulary”), and may also include specific eligibility requirements for each medication. Out of pocket costs will vary. 

Zepbound offers savings coupons for eligible individuals to access the autoinjector pens.  Another option is to use Zepbound vials available through Lily Direct cash-pay pharmacy in 2.5, 5, 7.5 and 10 mg vials with a valid prescription. This cash-pay option offers transparent pricing and may improve medication access for those without insurance coverage, or for those who are not eligible for coverage under their specific plan.  There are also cash pay options for Contrave through certain mail order pharmacies. 

When a provider may recommend Contrave or Zepbound

Both Contrave and Zepbound can be effective medications to help patients lose weight and maintain a healthy weight long-term in combination with lifestyle changes. Since obesity is a chronic disease, medications used to treat obesity typically need to be continued long-term, otherwise patients are at risk for regaining the weight that was lost.

Choosing a weight loss medication is dependent on multiple factors including:

• Weight loss history
• Health history
• Cost and coverage
• Medication contraindications
• Personal circumstances and preferences

For anyone taking Zepbound or Contrave, it’s important to remember that medication is most effective in conjunction with lifestyle changes that include behavior modifications, changes in diet, and increased physical activity. 

Contrave vs Zepbound in a personalized weight loss plan

Interested in starting Contave or Zepbound? Be sure to discuss your options with a medical weight loss expert! At Form Health, patients work 1:1 with a doctor who is board certified in obesity medicine and, if appropriate, will carefully review FDA-approved medication options that are safe for you and your needs. You’ll also work with a specialized Registered Dietitian to develop a personalized weight loss plan just for you addressing behavioral health, nutrition, and physical activity.

Find out if you are eligible by taking our quiz or send a message to get in touch with us directly at info@formhealth.co.

Zepbound®  and their delivery device bases are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

Contrave® is a registered trademark of Currax Pharmaceutical LLC.