Contrave is approved for long-term weight management, works through the brain's reward and appetite circuits rather than the gut hormones GLP-1 drugs copy, and costs a fraction of a GLP-1 at its maker's price. Its trials put the average loss at roughly 4 to 8% of body weight over a year, a few points more than placebo. Those trials also lost almost half of their participants before the end, and the large study meant to settle its heart safety was stopped early before it could answer the question. A replacement trial is due to finish in 2029.
This page reads the US Contrave label (effective 10 November 2025, read 3 November 2026), its trials and the maker's price page, and sets the GLP-1 figures this site already reports beside them, each with its population. It does not rank the medicines. The full set of non-GLP-1 options is on GLP-1 alternatives.
What Contrave is
Each extended-release tablet holds naltrexone 8 mg, an opioid antagonist used on its own for alcohol and opioid dependence, and bupropion 90 mg, the antidepressant sold as Wellbutrin and as the smoking aid Zyban. FDA approved the combination on 10 September 2014 (NDA 200063). The label's indication is long-term weight reduction and maintenance, with diet and physical activity, in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition. Strengths are listed here as product facts.
Two limits are printed with the indication: the effect on cardiovascular illness and death "has not been established", and combining it with any other bupropion product is contraindicated. The label's dosing section builds in a 12-week checkpoint: if a person has not lost at least 5% of their starting weight after 12 weeks at the maintenance dose, it says Contrave should be stopped, because meaningful weight loss is unlikely to follow.
The four COR trials
Four 56-week, double-blind, placebo-controlled trials enrolled 4,536 people. Across them the mean age was 46, 83% were women and the mean BMI was 36. All arms received diet and activity advice; COR-BMOD added 28 group counselling sessions.
| Trial | Population | People (Contrave / placebo) | Contrave | Placebo | Lost ≥5% (Contrave / placebo) |
|---|---|---|---|---|---|
| COR-I | Obesity or overweight with hypertension or dyslipidaemia | 538 / 536 | −5.4% | −1.3% | 42% / 17% |
| COR-II | Same population, published separately | 2:1 randomisation, 1,496 total | −6.4% | −1.2% | 50.5% / 17.1% |
| COR-BMOD | Same, plus intensive behavioural programme | 565 / 196 | −8.1% | −4.9% | 57% / 43% |
| COR-Diabetes | Type 2 diabetes, BMI >27 | 321 / 166 | −3.7% | −1.7% | 36% / 18% |
Sources: Contrave label Table 6 (COR-I, COR-BMOD, COR-Diabetes; intention-to-treat with last observation carried forward); COR-II, Apovian et al., Obesity 2013 (week-56 figures from the abstract).
Three things in that table matter more than the headline:
- The placebo arm in COR-BMOD lost 4.9%. With intensive counselling the drug added 3.2 points. The drug's contribution is a few points on top of whatever the lifestyle programme achieves.
- People with type 2 diabetes lost the least, a 2.0-point difference. The same pattern appears in GLP-1 trials, where people with diabetes lose less than people without it.
- Dropout was very high. About 46% on Contrave and 45% on placebo withdrew before week 56, most within the first 12 weeks; 24% on Contrave stopped because of an adverse reaction, against 12% on placebo. The label's figures carry the last recorded weight forward for people who left, a method that tends to understate weight regain.
Beside the GLP-1 figures
No trial compares Contrave with a GLP-1 medicine. These are the closest figures from separate trials, with their populations:
| Medicine (trial) | Population | Weeks | Medicine | Placebo |
|---|---|---|---|---|
| Contrave (COR-I) | Obesity or overweight with a related condition | 56 | −5.4% | −1.3% |
| Contrave (COR-Diabetes) | Type 2 diabetes | 56 | −3.7% | −1.7% |
| Semaglutide 2.4 mg (STEP 1) | Obesity or overweight with a related condition, no diabetes | 68 | −14.9% | −2.4% |
| Tirzepatide 15 mg (SURMOUNT-1) | Obesity or overweight with a related condition, no diabetes | 72 | −20.9% | −3.1% |
| Qsymia 7.5 mg/46 mg (label Study 2) | Obesity or overweight with two related conditions | 56 | −7.8% | −1.2% |
Sources: Contrave label; STEP 1; SURMOUNT-1; Qsymia label. The trials differ in length, era and how people who stopped were counted, so the gaps are approximate. The two GLP-1 molecules' own head-to-head is on tirzepatide vs semaglutide, and Qsymia's record is on Qsymia.
Side effects, from the label
The label's safety pool covers 2,545 people on Contrave and 1,515 on placebo for up to 56 weeks.
| Adverse reaction | Contrave | Placebo |
|---|---|---|
| Nausea | 32.5% | 6.7% |
| Constipation | 19.2% | 7.2% |
| Headache | 17.6% | 10.4% |
| Vomiting | 10.7% | 2.9% |
| Dizziness | 9.9% | 3.4% |
| Insomnia | 9.2% | 5.9% |
| Dry mouth | 8.1% | 2.3% |
| Diarrhoea | 7.1% | 5.2% |
| Hot flush | 4.2% | 1.2% |
| Tremor | 4.0% | 0.7% |
| Tinnitus | 3.3% | 0.6% |
Source: Contrave label Table 3. The most common reasons for stopping were nausea (6.3%), headache (1.7%) and vomiting (1.1%). Nausea is the side effect it shares with GLP-1 drugs; the rates for those are on GLP-1 nausea.
The warnings that set it apart:
- Boxed warning — suicidal thoughts and behaviours. It comes from bupropion: antidepressants raised that risk in children, adolescents and young adults in short trials. Contrave is not approved for anyone under 18. How the GLP-1 class's own label language on mood has changed is on GLP-1 and depression.
- Seizures. Bupropion lowers the seizure threshold. The label puts seizures at about 0.1% on Contrave vs 0% on placebo, says the risk is dose-related, and says the tablets should not be taken with a high-fat meal because that sharply raises exposure to both drugs.
- Blood pressure and heart rate. In the trials, mean blood pressure on Contrave rose about 1 mmHg at weeks 4 and 8, while on placebo it fell 2 to 3 mmHg; the largest gaps were in the first 12 weeks.
- Opioids. Naltrexone blocks opioid painkillers and can trigger withdrawal in people using them.
- Liver and eyes. The label lists hepatitis with naltrexone exposure and angle-closure glaucoma with antidepressants.
Contraindications, per the label: uncontrolled hypertension; seizure disorder or past seizures; any other bupropion product; current or past bulimia or anorexia nervosa; chronic opioid use or acute opioid withdrawal; abrupt withdrawal from alcohol, benzodiazepines, barbiturates or anti-seizure drugs; MAO inhibitors within 14 days; known allergy to its ingredients.
The heart-safety question, still open
FDA required a cardiovascular outcome trial. LIGHT enrolled 8,910 people at raised cardiovascular risk (85% with diabetes). An interim analysis at 25% of planned events showed fewer major heart events on Contrave (0.8% vs 1.3%); the trial then ended in what its published report calls an "unanticipated early termination". By 50% of events the difference had narrowed (2.0% vs 2.3%, hazard ratio 0.88), too early to test whether the drug met the safety margin set in advance. The trial's own authors concluded that Contrave's cardiovascular safety "remains uncertain" and needs a new trial (Nissen et al., JAMA 2016; NCT01601704). A second attempt (NCT02638129) was terminated with 67 people enrolled.
The replacement, INFORMUS (NCT06098079, sponsored by Currax Pharmaceuticals), started on 3 January 2024, has about 8,600 participants, is active and no longer recruiting, and estimates primary completion in January 2029 (ClinicalTrials.gov, record updated 31 March 2026). Until it reports, the label's line stands. The GLP-1 class, by contrast, has completed outcome trials; SELECT is summarised on GLP-1 benefits.
The two halves
Contrave is two older drugs in one tablet, and people often search for each on its own. Neither half has a weight-loss indication by itself: bupropion is sold as an antidepressant (Wellbutrin) and a smoking aid (Zyban), and naltrexone for alcohol and opioid dependence — its own obesity trials, from 1985, are on naltrexone and weight loss. The label's weight trials tested only the extended-release pair at its combined strengths, so the COR results describe the combination, not either drug alone. The bupropion-alone record, including the label's weight table for the antidepressant, is on Wellbutrin and weight loss.
What it costs
The maker's site, read 3 November 2026, states:
| Route | Price stated |
|---|---|
| CurAccess home-delivery programme (cash or uninsured) | $99 a month, free shipping |
| Retail pharmacy with the Contrave coupon card, insurance not covering it | no more than $199 a month |
| Insurance that covers it | "as little as $0" via the partner programme |
| Maker's online prescriber route | $45 consultation fee if prescribed |
Eligibility terms apply, and the maker notes its online service is not available in Louisiana. For comparison, the cash prices of GLP-1 medicines run from about $149 to $1,349 a month depending on product and route; the dated ladder is on GLP-1 cost.
What the record does not show
- Whether Contrave reduces or raises heart attacks and strokes. LIGHT could not answer it; INFORMUS is due in 2029.
- Results beyond 56 weeks in a placebo-controlled trial on the label.
- Any comparison with a GLP-1 medicine, or data on combining them. No trial is on either label.
Contrave is a prescription medicine with a boxed warning. Whether it, a GLP-1 medicine or neither fits a person's health and history is a decision for their prescriber.
Sources
- CONTRAVE (naltrexone HCl and bupropion HCl) extended-release tablets, US prescribing information, Nalpropion Pharmaceuticals, effective 10 November 2025, set ID 485ff360-32c8-11df-928b-0002a5d5c51b (openFDA drug label record), read 3 November 2026 — boxed warning, sections 1, 2, 4, 5.3, 5.5, 6.1, 14.
- Drugs@FDA (openFDA), NDA 200063, CONTRAVE, original approval 10 September 2014, read 3 November 2026.
- Apovian CM et al. "A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II)." Obesity 2013;21(5):935–43, doi:10.1002/oby.20309, PMID 23408728.
- Nissen SE et al. "Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors." JAMA 2016, doi:10.1001/jama.2016.1558, PMID 26954408.
- ClinicalTrials.gov records NCT01601704 (LIGHT, terminated), NCT02638129 (terminated, 67 enrolled), NCT06098079 (INFORMUS, active, not recruiting; record updated 31 March 2026), read 3 November 2026.
- contrave.com, home and savings pages, read 3 November 2026.
- Wilding JPH et al., NEJM 2021, PMID 33567185 (STEP 1). Jastreboff AM et al., NEJM 2022, PMID 35658024 (SURMOUNT-1). QSYMIA prescribing information, Vivus, effective 22 April 2026 — section 14.