Wegovy causes far more weight loss. In their main trials, weekly Wegovy injections cut body weight by 14.9% vs 2.4% on placebo, while Contrave, a twice-daily naltrexone-bupropion pill, cut it by 6.1% vs 1.3%. Being a pill is no longer Contrave’s edge: a daily Wegovy pill was approved in December 2025 and produced 13.6% loss.
Contrave versus Wegovy is a real choice between two approved weight-loss medications — not the same molecule in different packaging, but genuinely different drugs that work in different ways and produce very different results. The honest comparison comes down to effectiveness versus form.
Two different mechanisms
Contrave combines two old drugs: naltrexone (an opioid-receptor blocker) and bupropion (an antidepressant). Together they act on the brain’s appetite and food-rewardcircuits, taken as a pill twice daily. Wegovy is semaglutide, a GLP-1 receptor agonist — a once-weekly injection that slows gastric emptying and powerfully reduces appetite through gut-hormone signaling. Different targets, very different potency — and different safety profiles: the bupropion half is what gives Contrave a neuropsychiatric warning and a seizure contraindication a GLP-1 does not carry, which we detail in the Contrave side-effect and warning breakdown.
The weight-loss gap
The effectiveness difference is large. In its pivotal COR-I trial (1,742 adults, 56 weeks), Contrave at the approved dose produced about 6.1% weight loss versus 1.3% on placebo; only half of participants completed the full 56 weeks.[1] Wegovy, in the STEP 1 trial (1,961 adults, 68 weeks), produced about 14.9% weight loss versus 2.4% on placebo.[2] The newer once-daily Wegovy pill (oral semaglutide 25 mg) produced 13.6% vs 2.2% on placebo at 64 weeks in its OASIS 4 trial, close to the injection.[3]That’s roughly 2.5 times more weight loss with Wegovy — a clinically major difference, not a rounding error.
- Wegovy (semaglutide 2.4 mg)14.9%
- Contrave (naltrexone-bupropion)6.1%
| Wegovy (semaglutide) | Contrave (naltrexone-bupropion) | |
|---|---|---|
| Type | GLP-1 injection or daily GLP-1 pill | Oral combination pill |
| Mechanism | Gut-hormone appetite signaling | Appetite + food-reward circuits |
| Dosing | Pen once weekly; pill once daily | Twice daily |
| Weight loss (trial) | ~14.9% (pen); ~13.6% (pill) | ~6.1% |
| Needle-free? | Pill: yes; pen: no | Yes |
The honest verdict
For maximum weight loss, this isn’t close: Wegovy produced roughly 2.5 times the weight loss of Contrave in their respective trials.[1][2] If effectiveness is the priority and a weekly injection or daily pill is acceptable, Wegovy is the stronger choice. Contrave is the reasonable pick for people with reward-driven eating, people who can’t take a GLP-1, or people facing GLP-1 coverage barriers. To compare Wegovy against the tirzepatide brand, see Zepbound vs Wegovy; for the older injectable, Wegovy vs Saxenda; and for cost and access, our Wegovy cost guide and provider comparison.