Contrave vs Ozempic: full comparison for weight loss

Contrave and Ozempic attack weight loss from completely different angles. Contrave is an oral pill that targets the brain’s reward and hunger centers using naltrexone and bupropion. Ozempic is an injectable GLP-1 receptor agonist that changes how your gut communicates with your brain. Ozempic produces roughly twice the weight loss, but Contrave costs less and doesn’t require injections. The right choice depends on your goals, your budget, and what you’re willing to tolerate.

For broader context on GLP-1 medications and how they compare to other weight loss peptides, start with our main guide.

Quick comparison table

Feature	Contrave	Ozempic (semaglutide)
Drug class	Naltrexone/bupropion combination	GLP-1 receptor agonist
Mechanism	Reduces food cravings via opioid and dopamine pathways	Slows gastric emptying, reduces appetite, improves insulin
FDA-approved for	Chronic weight management	Type 2 diabetes (off-label for weight loss)
Administration	Oral tablets, twice daily	Subcutaneous injection, once weekly
Average weight loss	5-8% of body weight over 56 weeks	~14.9% over 68 weeks
Common side effects	Nausea, constipation, headache, insomnia	Nausea, diarrhea, vomiting, constipation
Monthly cost (retail)	$500-$840	$969
Savings programs	CurAccess: $99/month or less	Novo Nordisk: $199-$499/month self-pay
Controlled substance	No	No
Injection required	No	Yes

Key differences

The most important difference: Ozempic produces about twice the weight loss percentage as Contrave in clinical trials. The second most important difference: Contrave is a pill, and Ozempic is a weekly injection.

Contrave was FDA-approved for chronic weight management in 2014. It combines two existing drugs: naltrexone (an opioid antagonist used in addiction medicine) and bupropion (an antidepressant that also reduces appetite). Together, they target the hypothalamus and the mesolimbic reward system, reducing both physical hunger and the psychological drive to eat [1].

Ozempic contains semaglutide, a GLP-1 receptor agonist approved for type 2 diabetes in 2017 and widely used off-label for weight loss. Its FDA-approved weight loss version, Wegovy, uses a higher dose of the same molecule [2].

How Contrave works

Contrave hits two targets in the brain simultaneously.

Bupropion stimulates pro-opiomelanocortin (POMC) neurons in the hypothalamus, which signal fullness and reduce appetite. On its own, bupropion produces modest weight loss. The problem is that POMC neurons also release beta-endorphins that act as a feedback brake on the appetite-suppressing signal.

That’s where naltrexone comes in. By blocking opioid receptors, naltrexone prevents that feedback brake from engaging. The result: bupropion’s appetite-suppressing effect lasts longer and works more powerfully than either drug alone [1].

In the COR-I trial, participants taking Contrave (naltrexone 32 mg/bupropion) with lifestyle modifications lost an average of 6.1% of body weight over 56 weeks, compared to 1.3% with placebo. About 48% of Contrave users lost at least 5% of their body weight, versus 16% on placebo [3].

Those numbers are respectable for an oral medication but well below what GLP-1 drugs achieve.

Contrave is taken as two tablets twice daily (a total of four tablets per day at full dose). The titration takes about 4 weeks: you start with one tablet in the morning, then add a second each week until you reach the full dose of two morning and two evening tablets. Skipping the titration increases nausea risk significantly.

How Ozempic works

Semaglutide mimics GLP-1, a hormone your intestines release after eating. It works through three parallel mechanisms: slowing how quickly food leaves your stomach, suppressing appetite signals in the brain, and improving insulin secretion.

The practical effect is that people eat less, feel satisfied sooner, and spend less time thinking about food between meals.

In the STEP 1 trial (using the 2.4 mg Wegovy dose), semaglutide produced 14.9% weight loss over 68 weeks. At Ozempic’s lower dose ceiling of 2.0 mg, weight loss typically ranges from 10-15% [4]. For a deeper look at semaglutide, see our guide on how peptides work for fat loss.

The weight loss difference between Contrave and semaglutide is substantial: roughly 5-8% vs 10-15% for comparable treatment durations.

To put that in real numbers: a 220-pound person on Contrave might lose 11-18 pounds over a year. On semaglutide, the same person might lose 22-33 pounds. For patients who need significant weight loss to resolve conditions like sleep apnea or metabolic syndrome, that gap matters.

Side effects comparison

Both medications cause nausea as their most common side effect, but the rest of the profiles diverge.

Contrave side effects reflect its dual mechanism:

• Nausea (32%)
• Constipation (19%)
• Headache (18%)
• Vomiting (10%)
• Dizziness (10%)
• Insomnia (9%)
• Dry mouth (8%)

Contrave carries a boxed warning about suicidal thoughts and behaviors associated with bupropion, the same warning that applies to all bupropion-containing products. It’s contraindicated in patients with seizure disorders, eating disorders (bulimia/anorexia), or those taking opioid medications [1].

Ozempic side effects are primarily gastrointestinal:

• Nausea (20-44%)
• Diarrhea (18-30%)
• Vomiting (7-24%)
• Constipation (14-24%)

Ozempic’s GI side effects are worst during the first weeks of dose escalation and typically improve. It carries a boxed warning about thyroid C-cell tumors (from animal studies) and rare risks of pancreatitis and gallbladder disease [2].

A meaningful difference: Contrave can interfere with opioid pain medications because naltrexone blocks opioid receptors. If you take opioid-based painkillers or might need them for a planned surgery, Contrave is not a good fit.

Long-term tolerability data favors Ozempic slightly. In the COR trials, about 24% of Contrave patients discontinued due to adverse events, compared to 7-8% in the STEP semaglutide trials [3][4]. The higher dropout rate with Contrave is largely driven by persistent nausea and headaches that don’t always resolve.

Cost comparison

Contrave: Retail price runs $500-$840 per month depending on the pharmacy. The manufacturer’s CurAccess savings program can reduce this to $99/month or less for eligible patients, with or without insurance [5].

Ozempic: List price is $969 per month. Novo Nordisk offers self-pay pricing from $199 for the first two fills, then $349-$499/month depending on dose. With commercial insurance, copays can drop to $25/month [6].

Compounded semaglutide: $150-$350 per month through telehealth prescribers. For patients choosing between an $840/month brand pill and a $200/month compounded injectable, the math often favors semaglutide on both cost and efficacy.

Check pricing for compounded semaglutide →

Who should choose which

Contrave may be better if:

• You strongly prefer pills over injections
• You also struggle with food cravings or emotional eating (naltrexone targets reward-driven eating)
• You have mild depression (bupropion is an antidepressant)
• Your BMI is 27-35 and you’re looking for moderate weight loss
• You cannot take GLP-1 medications due to contraindications

Ozempic / semaglutide may be better if:

• You want the strongest weight loss results available
• You have type 2 diabetes or prediabetes
• You take opioid medications (rules out Contrave)
• You have cardiovascular risk factors (semaglutide reduced CV events by 20% in the SELECT trial)
• You’re okay with weekly injections
• You want access to compounded versions at lower cost

Consider compounded semaglutide if:

• Brand-name Ozempic is too expensive
• Your insurance doesn’t cover GLP-1 medications for weight loss
• You want 2-3x the weight loss of Contrave at a comparable price point

How they perform together with lifestyle changes

Both medications are meant to be combined with diet and exercise, not used as standalone treatments. In clinical trials, all participants received lifestyle counseling alongside the medication.

The STEP trials used modest calorie reduction (500 kcal/day deficit) and 150 minutes of weekly physical activity. The COR trials used similar lifestyle interventions. The medications amplify the effects of these changes rather than replacing them.

Patients who combine either medication with a structured weight loss program tend to see better and more sustained results than those relying on medication alone.

FAQ

Is Contrave or Ozempic more effective for weight loss?▼

Ozempic produces significantly more weight loss. Clinical trials show 10-15% body weight reduction with semaglutide versus 5-8% with Contrave over roughly similar timeframes. No head-to-head trial has directly compared them, but the gap is consistent across their respective trial programs.

Can you take Contrave and Ozempic together?▼

There’s no published data on combining Contrave with semaglutide. Some providers prescribe them together off-label, reasoning that different mechanisms might compound the effect. But this increases side effect risk, particularly nausea, and there’s no clinical evidence supporting the combination. Ask your provider about the risks before considering this.

Does Contrave work for emotional eating?▼

Better than most weight loss drugs, actually. Naltrexone blocks opioid receptors in the brain’s reward system, which can reduce the pleasure response to comfort eating. If your weight gain is driven more by cravings and reward-seeking behavior than by physical hunger, Contrave’s mechanism is more directly targeted at that problem than semaglutide.

Is there a generic version of Contrave?▼

As of 2026, there’s no generic Contrave approved in the US. However, naltrexone and bupropion are individually available as generics. Some providers prescribe them separately at a fraction of Contrave’s cost, though the dosing and release formulation differ from the branded combination.

What about Wegovy vs Contrave?▼

Wegovy is semaglutide 2.4 mg, the FDA-approved weight loss version of the Ozempic molecule. It produces 14.9% weight loss at 68 weeks. The comparison to Contrave is the same as Ozempic but slightly more favorable to semaglutide since Wegovy uses a higher dose. See our page on peptide therapy pricing for cost breakdowns.

Which has fewer side effects, Contrave or Ozempic?▼

Both cause nausea at comparable rates. Contrave adds insomnia, headaches, and the bupropion-related suicidality warning. Ozempic adds GI symptoms like diarrhea and vomiting but those tend to resolve over time. Neither has a clear advantage on tolerability. The decision usually comes down to which side effect profile concerns you less.

Find out which GLP-1 medication is right for you →

References

1. FDA. Contrave (naltrexone/bupropion) prescribing information. Revised 2023.
2. FDA. Ozempic (semaglutide) prescribing information. Revised 2024.
3. Greenway FL, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I). Lancet. 2010;376(9741):595-605.
4. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
5. GoodRx. 6 ways to save on Contrave for weight loss. Updated January 2026.
6. GoodRx. Ozempic 2026 prices, coupons, and savings tips. Updated 2026.