Contrave vs. Wegovy—Which Is Better for Weight Loss?
- By Lauren Bedosky
- February 28, 2024
History has seen many legendary face-offs: Ali vs. Frazier, PlayStation vs. Xbox, Coke vs. Pepsi. Thanks to the growing interest in prescription medications for weight loss, we can add another battling duo to the list: Contrave vs. Wegovy.
Contrave and Wegovy are FDA-approved medications that are often prescribed for those struggling with obesity and metabolic syndrome and who find it challenging to lose weight by just modifying lifestyle factors (1).
“Both medications act on appetite-regulating centers of the brain to reduce food cravings and hunger,” says Dan Maselli, M.D., a board-certified internal medicine, gastroenterology, and obesity medicine physician.
Still, Contrave and Wegovy are different classes of drugs and come in different forms (one is an injectable and the other a tablet). Here, doctors explain how both drugs work, their potential side effects, and which one is generally most effective for weight loss.
About the Experts
Dan Maselli, M.D., a board-certified internal medicine, gastroenterology, and obesity medicine physician and the associate director of research for True You Weight Loss, a weight loss center in Cary, North Carolina.
Dina Peralta-Reich, M.D., a board-certified obesity medicine and pediatrics physician and the founder and director of New York Weight Wellness Medicine, a clinical practice that helps patients address eating disorders, weight maintenance, and issues related to overweight and obesity.
Contrave vs. Wegovy
At first glance, Contrave and Wegovy appear similar, especially considering both are meant for someone with a body mass index (BMI) of 30 or greater, a standard measurement for obesity (2) or a BMI of 27 or greater with a weight-related health problem. But if you take a closer look, you’ll discover there are a few key differences, including how they’re taken and why someone may be prescribed the drug.
What is Contrave?
Contrave is an oral treatment that blends two medications: naltrexone and bupropion (3). “Individually, bupropion is used to treat depression and used for smoking cessation, and naltrexone helps treat certain substance misuse, like tobacco and alcohol,” Maselli says.
How these medications cause weight loss when combined is still somewhat of a mystery, but experts theorize that the combo touches the brain’s reward centers: “Bupropion affects the pathways of two neurotransmitters, dopamine and norepinephrine, which are used in brain areas that process appetite and reward, and naltrexone tends to boost and reinforce this effect,” Maselli says.
Together, bupropion and naltrexone tell your reward center that you’re satiated, which helps to stop incessant cravings (2). This, in part, helps you reduce food intake and ultimately, enables you to lose weight in combination with other healthy lifestyle changes, including exercise and a reduced-calorie diet (3).
Research published in Pharmacy and Therapeutics suggests patients with obesity can lose at least 5 percent of their body weight after using Contrave for 12 weeks—and as much as 11.5 percent after 56 weeks. (3)
What is Wegovy?
The injectable Wegovy is one of the newest medications to be approved for weight loss by the FDA (Contrave was the first one, approved in September 2014) (4).
Wegovy’s active ingredient is semaglutide, which belongs to a class of medications known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs). (5) Semaglutide mimics GLP-1, a gut hormone that slows stomach emptying so food takes longer to travel through your digestive tract (5). This decreases your appetite and helps you feel fuller faster, says Dina Peralta-Reich, M.D., a board-certified obesity medicine physician. In addition, it acts directly on the brain to decrease appetite.
Research shows this mimicking effect leads to weight loss—if you pair it with a reduced-calorie diet and increased physical activity.
In a randomized controlled clinical trial published in 2022, people lost an average of 15.2 percent of their starting body weight with semaglutide over a two-year period (6). An earlier trial in The New England Journal of Medicine found similar effects: Folks lost an average of 14.9 percent of their starting body weight with semaglutide over 68 weeks (7).
Wegovy may also offer benefits for people with obesity and type 2 diabetes. In one clinical trial published in The New England Journal of Medicine in 2016, patients with obesity and type 2 diabetes lost an average of 10.8 pounds and lowered their A1C (a measurement of average blood sugar levels) by 1.4 percent after taking 1 mg of semaglutide for 104 weeks (8).
Learn more About Weight Loss Meds
Contrave Side Effects
Both weight loss medications come with potential side effects.
According to Maselli, Contrave’s most common side effects include (9):
- Headache
- Nausea or vomiting
- Constipation
- Dizziness
- Fatigue
- Sleep issues
- Dry mouth
Maselli says you can dodge most of these side effects by starting a low dose of Contrave and gradually build to the maximum dose (two tablets twice daily; each tablet has 8 milligrams of naltrexone and 90 mg of bupropion) over three to four weeks.
Some people aren’t good candidates for Contrave, including those with uncontrolled high blood pressure or seizure disorder, and those who use opioids or antidepressants known as monoamine oxidase inhibitors, Maselli notes.
Wegovy Side Effects
Maselli lists these common symptoms of Wegovy (10):
- Bloating
- Nausea and vomiting
- Constipation or diarrhea
- Headache
- Fatigue
Similar to Contrave, you’ll start with the lowest dose, though the ramp-up with Wegovy takes a bit longer. According to Maselli, you’ll gradually increase your dose every four weeks until you reach the maximum dose of 2.4 mg a week after 20 weeks.
People with pancreatitis or gallbladder problems (including gallstones) should steer clear of Wegovy (4). The drug can also cause low blood sugar, kidney injury, diabetic retinopathy (diabetes-related eye damage), increased heart rate, and suicidal thoughts (4).
Wegovy vs. Contrave: Which is More Effective?
Among the two drugs, experts say the one that will be most effective for you will depend on your needs. Your doctor can help you determine which weight loss medication is more appropriate.
“In adults with obesity, without type 2 diabetes, weight loss is typically about 15-16 percent of starting body weight over the course of a year with Wegovy,” Maselli says. On the contrary, Contrave has been shown to help folks lose 5-8 percent of their body weight over the same amount of time, he adds.
Peralta-Reich says the fact Wegovy is taken as a weekly shot also makes it more effective than Contrave, which has to be taken twice a day. “It’s easier for patients to be consistent, and we know we need consistency to see results,” she explains.
Maselli added one caveat: Contrave and Wegovy have yet to be pitted head-to-head in a large, randomized controlled trial—aka, the gold standard evidence when claiming the effectiveness of any medical intervention.
Also, keep in mind that while one medication may be more effective on paper, the best option for you will depend on your lifestyle, medical history, and insurance coverage.
Regardless of which medication your doctor thinks will work best for you, weight loss medications work best paired with lifestyle changes. “Eating good caloric energy is necessary,” Peralta-Reich says.
In other words, just because your appetite isn’t raging anymore doesn’t mean you should simply downsize your portions—you should also ensure those portions consist of fruits, vegetables, high-fiber carbs, lean proteins, and heart-healthy fats.
The Bottom Line
While Contrave and Wegovy reduce appetite and prompt weight loss, they reach their destination via different routes. Contrave contains naltrexone and bupropion, a combination that may affect the brain’s reward centers to curb appetite. Wegovy, is an injection made of semaglutide, a compound that mimics a satiety-inducing gut hormone that acts on the brain to reduce appetite. Research suggests that Wegovy may be more effective for weight loss, but your medical history and needs will ultimately dictate which medication is the right fit for you.
References
1. Mayo Clinic. Prescription weight-loss drugs.
2. Obesity Medicine Association. Top Weight Loss Medications.
3. Sherman Matthew, et al. (2016). Naltrexone/bupropion ER (Contrave).
4. U.S. Food and Drug Administration (FDA). FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014.
5. UCLA Health. Semaglutide for weight loss – what you need to know.
6. Garvey WT, et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.
7. Wilding JPH, et al. (2021). Once-Weekly Semaglutide in Adults With Overweight or Obesity.
8. Marso SP, et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
9. Mayo Clinic. Naltrexone and Bupropion (Oral Route).
10. Mayo Clinic. Semaglutide (Subcutaneous Route).
