Contrave (naltrexone HCl + bupropion HCl ER): the 2026 GLP-1 guide

Overview

Contrave is a fixed-dose oral combination of naltrexone (an opioid receptor antagonist) and bupropion (a norepinephrine and dopamine reuptake inhibitor), FDA-approved on September 10, 2014 for chronic weight management in adults with obesity or overweight + comorbidity.

It is NOT a GLP-1 agonist. The mechanism is appetite/reward-circuit modulation in the hypothalamus, distinct from the satiety pathway that GLP-1s drive.

Clinical Efficacy

In COR-I (adults with obesity, no T2D), Contrave at the maintenance dose produced 6.1% weight loss at 56 weeks vs 1.3% on placebo. In COR-Diabetes, T2D patients saw 5.0% weight loss vs 1.8% placebo¹.

Contrave’s efficacy is in the modest range — meaningful but lower than the oral GLP-1 class (~12–16%) and substantially lower than tirzepatide (~22%).

Dosing & Titration

Each Contrave tablet is a fixed combination: 8 mg naltrexone + 90 mg bupropion. Titration is by tablet count, not strength:

• Week 1: 1 tablet AM, 0 PM
• Week 2: 1 tablet AM, 1 PM
• Week 3: 2 tablets AM, 1 PM
• Week 4+ (maintenance): 2 tablets AM, 2 PM (= 32 mg naltrexone / 360 mg bupropion daily)

Avoid taking with high-fat meals — bupropion absorption increases substantially, raising seizure risk¹.

Side Effects

Boxed Warning — Suicidal Thoughts and Behaviors

Contrave carries an FDA Boxed Warning for suicidal thoughts and behaviors. This is a class-wide bupropion warning (the same molecule is marketed as Wellbutrin for depression and Zyban for smoking cessation), not a Contrave-specific finding. The warning notes increased risk in children, adolescents, and young adults, and emphasizes monitoring during the first months of treatment¹.

Most common adverse reactions (Contrave 32/360 mg vs placebo)

Contraindications

• Uncontrolled hypertension
• Seizure disorder or history of seizures
• Use of other bupropion-containing products
• Bulimia or anorexia nervosa
• Chronic opioid use
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concomitant MAOI use (or within 14 days of stopping one)
• Known allergy to bupropion, naltrexone, or other Contrave components

2026 Availability

Contrave is widely covered as a Part D Tier 3 medication. Cash list price is approximately $650/month; commercial-insurance copay savings programs from the manufacturer typically bring this lower.

Contrave is NOT included on the Medicare GLP-1 Bridge program — the Bridge is restricted to GLP-1 receptor agonists with on-label chronic-weight-management indication.

For patients comparing oral options: see Foundayo (oral GLP-1, ~12-16% loss, $149/mo cash) and Wegovy Tablets (oral GLP-1, ~12-15% loss, $149/mo cash). Contrave’s role is as the non-GLP-1 oral alternative when GLP-1s aren’t tolerated, accessible, or wanted.