Contrave vs. Wegovy: Weight Loss, Safety, Cost, and Who Fits Each
Contrave produced a placebo-subtracted mean weight loss of 4.7% at one year in its phase 3 trials, while Wegovy produced an average 13.7% loss at 72 weeks in SURMOUNT-5. The two differ sharply in safety profile, dosing, and price.
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Contrave and Wegovy are both FDA-approved for chronic weight management, but they are different drugs in different classes, and the size of the average weight loss is not close. Contrave (naltrexone-bupropion) is approved for adults with a BMI of 30 or more, or 27 or more with a weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia [1][5]. Wegovy (semaglutide) is approved for adults with obesity, or overweight with a weight-related medical problem, and for adolescents ages 12 and older [7][10]. In pooled phase 3 trials, Contrave produced a placebo-subtracted mean weight loss of 4.7% at one year [4]. In SURMOUNT-5, Wegovy produced an average weight loss of 13.7% at 72 weeks [7]. Those figures come from separate trials of different lengths and populations, so they cannot be compared directly [4][7].
The safety profiles are also very different. Contrave carries a boxed warning for suicidal thoughts and behaviors and has a long list of contraindications, including seizure disorders and uncontrolled hypertension [2][5]. Wegovy’s common side effects are mostly gastrointestinal, such as nausea, vomiting, and diarrhea [10]. Contrave is a twice-daily pill; Wegovy is a once-weekly injection, and NovoCare also lists a Wegovy pill [5][10][12]. On price, Contrave runs from $20 to $199 a month depending on the program, while Wegovy pen self-pay pricing through NovoCare is $199 per month for the first two fills for new patients, then $349 per month [10][11][12].
What is Contrave and how is it thought to work?
Contrave is an extended-release, fixed-dose combination tablet containing 8 mg of naltrexone and 90 mg of bupropion [3][5]. Naltrexone is an opioid antagonist approved on its own to treat alcohol and opioid dependence [1][3]. Bupropion is an aminoketone antidepressant approved on its own for depression, seasonal affective disorder, and as an aid to smoking cessation [1][3][4].
The FDA approved Contrave in September 2014 [1][3][5]. The agency had declined approval in February 2011 pending a cardiovascular trial, after an advisory committee voted 13:7 in favor on December 7, 2010 [3][4]. The drug was developed by Orexigen and distributed by Takeda at approval; Currax Pharmaceuticals is the company behind it now [1][5][11].
The working theory: bupropion stimulates POMC neurons in the hypothalamus, which reduces food intake, but beta-endorphin feedback then inhibits those same neurons. Naltrexone blocks that feedback, which is thought to keep the effect going [3][4]. Preclinical data also point to actions on the mesolimbic dopamine reward circuit [2][3]. The label, the manufacturer, and published reviews all state that the exact neurochemical mechanism is not fully understood [2][3]. In a phase 2 trial, bupropion alone produced 2.7% weight loss at 48 weeks, compared with 5.0% to 6.6% for the combinations [4]. Contrave is brand-only and approved for adults only [10].
What is Wegovy and how is it different?
Wegovy is semaglutide, a once-weekly injectable GLP-1 receptor agonist approved for adults and adolescents ages 12 and older [10]. It slows the movement of food through the gut, reduces cravings and appetite, and increases fullness [10]. It is also indicated to lower the risk of heart problems in overweight or obese adults with heart disease, and to treat MASH (a form of fatty liver disease) with moderate-to-advanced fibrosis [10].
Contrave is in a different drug class from GLP-1 agonists [2]. NovoCare lists a Wegovy pill (tablets, 30 per bottle) alongside the pen [12]. In the SURMOUNT-5 trial, the Wegovy arm used a maximum tolerated dose of 1.7 mg or 2.4 mg, and 92.8% of participants received at least one dose of 2.4 mg [7].
How much weight did Contrave produce in its trials?
The Contrave Obesity Research (COR) program consisted of four phase 3 trials (COR-I, COR-II, COR-BMOD, and COR-DM) enrolling nearly 4,500 patients, with co-primary endpoints at 56 weeks [1][4][6]. Key results:
| Trial | Population | Contrave (ITT) | Placebo (ITT) |
|---|---|---|---|
| COR-I | Adults without diabetes | 5.4% (12 lb) | 1.3% (3 lb) [2][6] |
| COR-BMOD | Adults with an intensive behavior program | 8.1% (~18 lb) | 4.9% (~11 lb) [2][6] |
| COR-DM | Adults with type 2 diabetes | 3.7% (8.5 lb) | 1.7% (4 lb) [1][6] |
In COR-I, completers lost 8.1% versus 1.8% for placebo, and 42% of the full treated group lost at least 5% of body weight versus 17% on placebo (62% vs 23% among completers) [1][2]. COR-BMOD included 28 group behavior-modification sessions over 56 weeks; completers lost 11.5% versus 7.3%, or 25 lb versus 16 lb [2][6]. In COR-DM, 36% lost at least 5% versus 18% on placebo, a placebo-subtracted difference of 2%, and HbA1c fell about 0.5 points more than placebo [1][4][6].
Pooled across the phase 3 program, the placebo-subtracted mean weight loss was 4.7% (range 3.2% to 5.2%) at one year, and the placebo-subtracted share of patients reaching 5% loss ranged from 26% to 33% [4]. The manufacturer summarizes this as 2 to 4 times more weight loss than diet and exercise alone [6]. During the trials, 46% of Contrave participants discontinued treatment versus 45% on placebo [6]. GoodRx summarizes the one-year data as about 40% of adults losing at least 5% and about 20% losing at least 10% [10]. Weight loss is typically noticeable about 4 weeks in [10]. The trials excluded people with cardiovascular, psychiatric, seizure, hepatic, or renal disease; participants were ages 18 to 65 (COR-DM to 70) with BMI 30 to 45 [4].
How much weight did Wegovy produce, and how big is the gap?
SURMOUNT-5 (NCT05822830) was a 72-week, open-label trial that randomized 751 adults without diabetes in the U.S. and Puerto Rico [7]. The Wegovy arm averaged 13.7% weight loss at 72 weeks, or 33.1 lb (15.0 kg); the Zepbound arm averaged 20.2% [7].
Wegovy responder rates were 60.5% reaching at least 10% loss, 40.1% reaching 15%, 27.3% reaching 20%, and 16.1% reaching 25% [7]. Average waist circumference fell 13.0 cm (5.1 in) [7]. GoodRx cites an average 15% loss after 16 months on Wegovy [10]. In SURMOUNT-5, 8.0% of Wegovy participants discontinued for adverse events [7].
The Contrave and Wegovy numbers cannot be compared directly: they come from separate trials of different durations (56 weeks versus 72 weeks) and different trial populations [2][6][7].
Where does Contrave rank among other weight-loss pills?
A network meta-analysis published in JAMA covered 28 trials, more than 29,000 patients, and five FDA-approved weight-loss drugs, all with at least one year of follow-up [8]. Only 23% of placebo patients reached a 5% loss, versus 44% to 75% on active drugs, which produced 3 to 19 lb more loss than placebo [8].
Phentermine-topiramate (about 9 times the odds of a 5% loss versus placebo) and liraglutide (about 6 times) were the most effective of the five [8]. Patients taking liraglutide and naltrexone-bupropion were the most likely to stop their medication because of side effects [8].
What safety issues does Contrave carry?
Contrave’s boxed warning covers suicidal thoughts and behaviors, based on the risk shown in children, adolescents, and young adults under 25 in short-term antidepressant trials; the label calls for monitoring in patients of all ages [1][2][5]. Contrave is not approved for major depressive disorder, other psychiatric disorders, smoking cessation, or use in pediatric patients [2][5][6]. Postmarketing reports with bupropion used for smoking cessation have included mood changes, psychosis, hostility, and suicidal ideation [2][5].
The contraindication list includes uncontrolled hypertension; seizure disorder or history of seizures; anorexia or bulimia; chronic opioid use or acute opiate withdrawal; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs; MAOI use within 14 days; other bupropion-containing products; and known allergy [2][5]. Seizure risk is dose-related, the total dose is capped at four tablets per day, and the label says to avoid taking it with high-fat meals [2][5].
Because of naltrexone, an opioid-free interval of 7 to 10 days is recommended before starting, and up to two weeks for people coming off buprenorphine or methadone; the label warns that trying to override the naltrexone blockade with large amounts of opioids can be fatal [2][3][6]. Other warnings include increases in blood pressure and heart rate (with greater risk in the first three months), hepatotoxicity, activation of mania, angle-closure glaucoma, and hypoglycemia in people with type 2 diabetes on insulin or sulfonylureas [2][5]. The effect on cardiovascular morbidity and mortality has not been established [2][5][6]. On pregnancy, the label states that weight loss may cause fetal harm and to discontinue when pregnancy is recognized; the pregnancy contraindication was removed from the label in August 2020 [5]. Contrave can also cause a false-positive urine test for amphetamines [5].
How do the side effects compare?
Contrave’s most common side effects (reported in at least 5% of patients) were nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%), dizziness (9.9%), insomnia (9.2%), dry mouth (8.1%), and diarrhea (7.1%) [2][5]. Placebo groups showed greater improvement in systolic blood pressure and pulse than the naltrexone-bupropion groups [4].
Wegovy’s common side effects include nausea, vomiting, and diarrhea, plus injection-site reactions; the serious risks GoodRx lists include pancreatitis, certain thyroid tumors, and stomach paralysis [10]. Wegovy can also change how the body absorbs other oral medications [10]. GoodRx advises avoiding alcohol with Contrave, and the Contrave label has an alcohol-use section [5][10].
How are the two taken day to day?
The Contrave label lays out a four-week escalation: one tablet in the morning in week 1; one in the morning and one in the evening in week 2; two in the morning and one in the evening in week 3; and two in the morning and two in the evening from week 4 onward, for a total of 32 mg naltrexone and 360 mg bupropion [3][5]. The tablets are not to be cut, chewed, or crushed, and are taken morning and evening [5].
The label says response should be evaluated after 12 weeks on the maintenance dose, and that Contrave should be discontinued if a patient has not lost at least 5% of baseline body weight [1][3][5]. The dose is capped at one tablet twice daily with CYP2B6 inhibitors, and lower doses apply with renal or hepatic impairment [3][5]. Bupropion inhibits CYP2D6, so drugs such as SSRIs, antipsychotics, metoprolol, and some antiarrhythmics may need dose reduction [3][5].
Wegovy is dosed once weekly, as a pen or a pill, while Contrave at full dose means four tablets a day [5][10][12]. Weight loss on Wegovy is usually noticeable about 4 weeks in [10].
What does each one cost?
All of the prices below are program prices with eligibility limits, not list prices [10][11][12].
| Product | Program | Price |
|---|---|---|
| Contrave | Commercial insurance copay card | As little as $20/month [10] |
| Contrave | Patient assistance (uninsured or underinsured) | $99 or less per month [10] |
| Contrave | GoodRx cash price (launched July 15, 2025) | $199/month at 70,000+ pharmacies [11] |
| Wegovy pen | NovoCare self-pay, new patients, 0.25 or 0.5 mg | $199/month for the first 2 fills, through December 31, 2026 [12] |
| Wegovy pen | NovoCare self-pay, ongoing | $349/month (0.25 to 2.4 mg); $399 for Wegovy HD 7.2 mg [12] |
| Wegovy pill | NovoCare self-pay | $149 (1.5 mg), $199 (4 mg), $299 (9 mg and 25 mg) per month [12] |
| Wegovy | Commercial insurance | As little as $25/month for up to 3 months, max $100/month savings, government beneficiaries excluded [12]; GoodRx cites as little as $0 with a savings card [10] |
GoodRx also lists $199 for the first two Wegovy fills and $349 after that [10]. Novo Nordisk states it may modify or cancel its programs at any time [12].
What do the 2026 ADA Standards of Care say about choosing?
The ADA’s 2026 Standards of Care in Overweight and Obesity, summarized by Medscape on April 27, 2026, sets weight-loss goals of at least 5% for all adults on obesity medication, at least 10% for conditions like MASH, HFpEF, and knee osteoarthritis, and at least 15% for severe complications such as obstructive sleep apnea [13].
For type 2 diabetes, GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists are the preferred medications, with tirzepatide, semaglutide, and liraglutide showing demonstrated benefit; naltrexone-bupropion, phentermine-topiramate, and orlistat are listed as potential benefit [13]. In the guideline’s table, semaglutide shows demonstrated benefit for ASCVD, HFpEF, MASH, hypertension, and prediabetes, while naltrexone-bupropion appears only in the type 2 diabetes row [13].
The ADA calls for shared decision-making that weighs cost, access, tolerability, and patient preferences, and for offering obesity medication as part of initial treatment for adults with or at high risk of obesity-related complications [13]. If goals are not met, the options listed are escalating the dose, switching or combining medications, intensifying lifestyle management, or considering bariatric surgery [13]. The guidance says to avoid obesity medications during pregnancy or breastfeeding [13]. Bupropion is listed as a non-weight-promoting alternative to weight-gaining antidepressants [13].
Who tends to fit each drug?
Contrave is designed to control cravings and reduce hunger, and GoodRx notes it may be especially useful for emotional eating [2][10]. It is an oral tablet taken twice a day at the target dosage and considered safe for long-term use, while phentermine is approved only for short-term use, and phentermine and Qsymia contain a stimulant and are controlled substances [10]. Contrave’s expected effect is about 5% placebo-subtracted weight loss, versus about 14% absolute loss for Wegovy in SURMOUNT-5 [4][7].
Wegovy lines up where a 10% to 15% loss is the target, or where ASCVD, HFpEF, MASH, or type 2 diabetes is present, per the ADA table [7][13]. Contrave is ruled out for people with a seizure history, an eating disorder, uncontrolled hypertension, chronic opioid use, or recent MAOI use [2][5]. GoodRx lists certain thyroid tumors among Wegovy’s serious risks [10]. Despite containing bupropion, Contrave is not approved for depression or smoking cessation [2][6]. On cost, Contrave runs $20 to $199 a month depending on coverage, versus $149 to $399 self-pay for Wegovy [10][11][12].
In short: Contrave delivered about 4.7% placebo-subtracted loss at one year, carries a boxed warning and a long contraindication list, and costs $99 or less through patient assistance or $199 cash through GoodRx [4][5][10][11]. Wegovy delivered 13.7% at 72 weeks in SURMOUNT-5, has mostly gastrointestinal side effects, and costs $199 to $349 self-pay for the pen [7][12]. The ADA places semaglutide in the demonstrated-benefit column for most obesity-related comorbidities, and naltrexone-bupropion in the potential-benefit column for type 2 diabetes only [13].
Sources
- HCPLive. FDA Approves Contrave for Weight Loss in Obese Adults. September 11, 2014.
- CONTRAVE (naltrexone HCl/bupropion HCl). For healthcare professionals.
- PubMed Central. Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults.
- PubMed Central. Naltrexone/Bupropion: An Investigational Combination for Weight Loss and Maintenance.
- US Food and Drug Administration. CONTRAVE (naltrexone hydrochloride and bupropion hydrochloride) extended-release tablets prescribing information. 2021.
- CONTRAVE. Results with CONTRAVE.
- Eli Lilly and Company. Zepbound (tirzepatide) showed superior weight loss over Wegovy (semaglutide) in complete SURMOUNT-5 results published in The New England Journal of Medicine. May 11, 2025.
- CardioSmart, American College of Cardiology. Study Confirms the Benefits of FDA Approved Weight Loss Pills. July 2016.
- US Food and Drug Administration. CONTRAVE (naltrexone hydrochloride and bupropion hydrochloride) extended-release tablets prescribing information. 2021.
- GoodRx. Phentermine alternatives: 6 weight-loss medications to consider.
- Currax Pharmaceuticals. Currax expands access to FDA-approved obesity treatment with brand name Contrave with new cash price available via GoodRx. July 15, 2025.
- NovoCare Pharmacy. Get your GLP-1 medications delivered with NovoCare Pharmacy.
- Medscape. Standards of care in overweight and obesity: pharmacologic treatment. ADA 2026 guideline summary. April 27, 2026.
Frequently asked questions
Is Contrave as effective as Wegovy?
The numbers are not directly comparable, because they come from separate trials of different lengths and populations. Contrave produced a pooled placebo-subtracted mean loss of 4.7% at one year in its phase 3 program. Wegovy produced an average 13.7% loss at 72 weeks in SURMOUNT-5, a 72-week open-label trial.
Can Contrave and Wegovy be taken together?
The Contrave label states that its safety and effectiveness in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established. The ADA guidelines list combining medications as one option when treatment goals are not met, alongside dose escalation, switching, or surgery.
How fast does Contrave work, and when is it stopped for non-response?
Weight loss on Contrave is typically noticeable about 4 weeks in. The label says response should be evaluated after 12 weeks on the maintenance dose, and that Contrave should be discontinued if at least 5% of baseline body weight has not been lost, since further clinically meaningful loss is unlikely.
Why does Contrave have a boxed warning?
Because it contains bupropion, the same active ingredient as some antidepressants. Antidepressants increased the risk of suicidal thoughts and behaviors in children, adolescents, and young adults under 25 in short-term trials, and the label calls for monitoring for worsening or emerging suicidality in patients of all ages.
Does Contrave help with depression or quitting smoking?
No. The label states Contrave is not approved for major depressive disorder, other psychiatric disorders, or smoking cessation, even though bupropion alone is approved for those uses. Postmarketing reports of serious neuropsychiatric events exist for bupropion used for smoking cessation.
Can you drink alcohol while taking Contrave?
GoodRx advises avoiding alcohol with Contrave, and the label includes an alcohol-use section. Abruptly stopping alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is also listed as a contraindication, and excessive alcohol use is flagged as a seizure risk factor.
Is Contrave a controlled substance?
No source lists Contrave as a controlled substance. Phentermine and Qsymia, by contrast, contain a stimulant and are controlled substances, and phentermine is approved only for short-term use, while Contrave is an oral tablet considered safe for long-term use.
How much does Contrave cost without insurance?
Uninsured or underinsured patients may qualify for the patient assistance program, which provides a month of medication for $99 or less. A GoodRx cash price of $199 per month, regardless of insurance status, launched July 15, 2025 at more than 70,000 pharmacies, with program limits applying.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.