The landscape of pharmacological obesity treatment is rapidly evolving, requiring healthcare providers to stay informed. Before 2012, the FDA had approved few weight loss medications. However, the 2020s witnessed a surge in the popularity of glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists). This was followed by the introduction of dual receptor agonists like Mounjaro (for type 2 diabetes) and Zepbound (for obesity). In 2024 alone, millions of adults used a GLP-1 medication for weight loss. The increasing availability of weight loss medications raises questions about which is the most effective and suitable for individual patients. The answer is multifaceted, and newer options are not always superior.
Determining a patient's eligibility for weight loss medications starts with assessing their Body Mass Index (BMI). A comprehensive discussion between the doctor and patient is crucial, considering the patient's current health status, existing medications, and family medical history. Weight loss results vary, typically ranging from 5% to 21% of body weight, with individual outcomes differing. It's important to note that most individuals regain weight upon discontinuing AOMs (anti-obesity medications). While some weight loss medications are exclusively approved for adults, certain medications like semaglutide and liraglutide are approved for children aged 12 and older with a BMI at or above the 95th percentile.
While GLP-1s have captured considerable attention, they represent the latest advancement in a long history of evolving weight loss medications. As more physiological mechanisms for weight gain are identified, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied and have shown increased adoption by physicians. Some weight loss drugs have been on the market longer, have generic alternatives, and tend to be more affordable. GLP-1s are notoriously costly. The Kaiser Family Foundation estimates the annual net price of Wegovy at $13,600 and are not covered by insurance.
Understanding Contrave
Contrave is a combination medication containing naltrexone and bupropion. Naltrexone is an opioid antagonist, while bupropion acts as an antidepressant. Together, these medications affect the reward center in the brain to decrease food cravings. They also work in the appetite control center of the brain to reduce appetite.
Understanding Ozempic
Ozempic, known generically as semaglutide, is a GLP-1 receptor agonist. It mimics gut hormones that the body naturally produces after meals. Similar to Contrave, Ozempic acts on the appetite control center of the brain to reduce appetite and on the reward center of the brain to reduce cravings.
Read also: Comparing Contrave and Phentermine
Ozempic also functions in the gut by slowing stomach emptying, promoting earlier and longer-lasting feelings of satiety. Furthermore, Ozempic enhances insulin sensitivity and improves blood sugar regulation by acting on the pancreas and other sites in the body.
Dosage and Administration
Dosage patterns for Contrave and Ozempic differ significantly.
Contrave Dosing
Contrave is available in tablet form for oral administration, with or without food. Each tablet contains 8 mg of naltrexone and 90 mg of bupropion. The typical starting dose is one tablet daily for the first week, gradually increasing by one tablet per day each week until reaching the full dose of two tablets twice daily by week four.
After the first week, dosing may then increase this way:
- Week 2: 1 tablet twice daily
- Week 3: 2 tablets in the morning and 1 tablet in the evening
- Week 4 and beyond: 2 tablets twice daily.
Ozempic Dosing
Ozempic is administered via a pen device as a subcutaneous injection once weekly. The initial dose is typically 0.25 mg weekly for four weeks, with subsequent monthly increases until reaching the maximum tolerated dose of either 1 or 2 mg weekly.
Read also: Weight Loss with Contrave and Topiramate
The dosing may progress this way:
- Month 2: 0.5 mg weekly
- Month 3: 1 mg weekly
- Month 4 and on: 2 mg weekly
Many patients choose to remain at the 1 mg dose long-term, depending on their response to the medication and any side effects experienced.
Weight Loss Results: Contrave vs. Ozempic
Contrave Weight Loss Results
Clinical trials have demonstrated that participants taking the maximum dose of Contrave for weight loss (32 mg naltrexone / 360 mg bupropion per day) in conjunction with healthy lifestyle changes experienced an average weight loss of 8.1% of their total body weight over 56 weeks, compared to 4.9% weight loss in participants receiving a placebo alongside healthy lifestyle interventions.
It's important to note that this percentage includes patients who discontinued Contrave early. Among participants who remained on Contrave for the entire 56 weeks, the average weight loss was higher, at 11.5%.
Ozempic Weight Loss Results
Ozempic has been studied in the treatment of people with type 2 diabetes and not specifically for weight loss. Wegovy has the same active ingredient as Ozempic, semaglutide, and has been studied in people with obesity but without diabetes, we can look at trials on Wegovy to help understand the probable response to Ozempic for people without type 2 diabetes. It is important to note that Wegovy and Ozempic have slightly different dosing. The dose of semaglutide used in Wegovy trials was 2.4 mg weekly, while Ozempic only goes up to 2 mg weekly dose.
Read also: Transformations with Ozempic
Clinical trials showed that patients taking Wegovy 2.4 mg weekly lost an average of 14.9% of their total body weight in 68 weeks when combined with healthy lifestyle changes vs 2.5% weight loss in participants receiving a placebo plus healthy lifestyle intervention. A follow-up study showed that this weight loss was sustained over 2 years (104 weeks) in participants who continued Wegovy, with 15.4% average weight loss at 2 years in the Wegovy group vs 2.6% in the placebo group. Again, these results are for Wegovy, the version of semaglutide FDA-approved for chronic weight management in individuals with obesity, rather than Ozempic, which is only FDA-approved for treating type 2 diabetes.
Data suggests that people with type 2 diabetes tend to lose less weight, on average, than people without type 2 diabetes. In a study of people with overweight or obesity and type 2 diabetes, Ozempic 2 mg weekly produced, on average, a 14.1 pound weight loss over 40 weeks. While these results are important to consider when choosing a treatment plan, weight loss results for Ozempic, Contrave or any other medications vary widely among individuals and can be affected by many factors, including:
- Other medical diagnoses
- Other medications
- Genetics
- Environment
- Lifestyle changes
A program that accounts for all these factors is crucial when choosing a medication as part of a comprehensive weight loss plan.
Side Effects
Side Effects of Contrave
Common side effects of Contrave include:
- Nausea
- Constipation
- Headache
- Vomiting
- Tiredness
- Dizziness
- Trouble sleeping
- Dry mouth
- Diarrhea
Contrave is initiated at a low dose and gradually increased to enhance tolerance and minimize side effects. It can elevate heart rate and blood pressure, necessitating close monitoring, particularly in patients with a history of hypertension. Mood should also be monitored closely while on Contrave, as this medication may cause mood disturbances and, very rarely, patients taking Contrave may experience suicidal ideation. Contrave may not be taken with certain prescription pain medications or during most surgical procedures. Patients taking Contrave should notify their healthcare provider right away should they experience any side effects from the medication or have upcoming procedures.
Side Effects of Ozempic
The most common side effects of Ozempic are gastrointestinal symptoms, including:
- Nausea
- Vomiting
- Constipation
- Diarrhea
- Stomach pain
- Tiredness
When combined with other blood-sugar-lowering medications, low blood sugar can occur, which may include symptoms such as:
- Lightheadedness
- Shakiness
- Sweating
- Blurred vision
- Irritability
For this reason, doses of insulin are often reduced prior to starting Ozempic to avoid the risk of low blood sugar. Rarely, cases of gallbladder disease and acute pancreatitis have been reported with this medication. There are also studies showing an increased risk of medullary thyroid cancer in rats while on Ozempic. People with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 should not take this medication. Patients should monitor for side effects and notify their healthcare provider immediately if they experience any while taking Ozempic.
FDA Approval
Contrave is FDA-approved for treating adults with obesity (BMI 30+) or with overweight (BMI 27+) and at least one weight-related medical condition, such as:
- Type 2 diabetes
- High blood pressure
- High cholesterol
Ozempic is FDA-approved for treating adults with type 2 diabetes. Ozempic, when used for weight loss in a person without type 2 diabetes, is being used off-label. prescriptions are considered off-label prescriptions. Ozempic has an additional FDA approval for lowering the risk of major cardiovascular events such as stroke, heart attack, or death in adults with type 2 diabetes and known heart disease. As noted above, Wegovy is a medication with the same active ingredient as Ozempic, semaglutide, which is FDA-approved for chronic weight management in individuals with obesity. Therefore, Ozempic is sometimes prescribed instead of Wegovy due to availability and insurance coverage.
Insurance Coverage
Insurance coverage for obesity management medications varies widely based on individual insurance plans. Most insurance companies that cover Ozempic and bupropion or Contrave require specific criteria to be met prior to approving these medications. With insurance coverage, many patients may pay less.
Ozempic Coverage
For those with prescription coverage for Ozempic, the manufacturer has a coupon program that can take up to $150 off of the copay each month to bring the cost as low as $25 for a 1-3 month supply. For those without insurance coverage, Ozempic can be quite costly at around $900-$1000 per month.
Choosing Between Contrave and Ozempic
Both Contrave and Ozempic can be highly effective medications in helping patients lose weight and maintain a healthy weight long-term. Because obesity is considered a chronic disease, medications to treat it usually need to be continued long-term, first to help with weight loss and then to assist with weight loss maintenance. Choosing an obesity management medication is an individualized decision made by a patient and their healthcare provider based on factors such as:
- A patientâs weight loss and health history
- A patientâs personal preferences
- Cost
- Other factors
A few notable scenarios in which a provider may suggest one of these medications over another include:
When a provider may recommend Ozempic
- If a patient has a diagnosis of type 2 diabetes or other insulin resistance syndrome with or without cardiovascular disease, a provider may suggest Ozempic as it is FDA-approved for type 2 diabetes and for reducing the risk of cardiovascular events.
- If a patient struggles with a lack of satiety with typical portions, Ozempic may be suggested to help with earlier and longer-lasting feelings of fullness.
When a provider may recommend Contrave
- If a patient struggles with depression, Contrave may be suggested as the bupropion component of Contrave can help with moods (although it is not FDA-approved for this use).
- If a patient struggles with significant cravings or emotional eating, Contrave may be suggested to help reduce these cravings (although Ozempic may also be helpful for craving reduction).
Additional Considerations
- The Role of Lifestyle Changes: All weight loss medications work best in the context of a healthy eating plan and exercise.
- Long-Term Use: Some weight management medications are designed for short-term use and others for long-term use. Those approved by the FDA for long-term use include orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide (Zepbound, Mounjaro).
- Medication Interactions: Older AOMs also have indications based on BMI and may be contraindicated for use with certain other medications.
- Compounded Medications: Some online healthcare providers claim to sell Ozempic, Wegovy, or Zepbound at reduced prices. However, the FDA warns against buying medications from any source other than a state-licensed pharmacy. In April 2025, they banned the sale of âcounterfeitâ semaglutide and tirzepatide. These medications are not made or packaged by the original manufacturers. Instead, they are compounded medications are not FDA-approved.
The Future of Obesity Medications
With fervent consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years. Pharmaceutical platform Ozmosi predicts one to two GLP-1 launches annually starting in 2026 specifically for obesity. Researchers continue to study hormones that play a role in appetite for other ways to target obesity with medication. Those of interest include not only GLP-1, but also peptide tyrosine-tyrosine (PYY) and cholecystokinin (CCK). With more options available, doctors will be increasingly able to personalize treatments. FDA-approved anti-obesity medications (AOMs) are safe, evidence-based therapies that target specific physiology to improve the disease and are most effective when used as part of a comprehensive treatment plan.