How does the weight loss efficiency of Wegovy compare to Contrave?

In major STEP trials, Wegovy led to about 15% weight loss over 68 weeks. Contrave (called Mysimba in the UK) generally achieves around 6–9% across pivotal studies. This means semaglutide tends to provide greater weight reduction than naltrexone/bupropion combinations.

Two very different medicines

Although both Wegovy and Contrave are used for weight management, they belong to very different drug families and work in different ways. Wegovy contains semaglutide, a GLP-1 receptor agonist that mimics a natural hormone to reduce appetite, slow digestion, and improve insulin release. Contrave, branded as Mysimba in the UK, combines naltrexone and bupropion, drugs originally used for addiction and depression. Together, they influence reward and craving pathways in the brain, aiming to reduce food cravings and emotional eating. The contrast in mechanisms explains why their effectiveness differs and why patients may respond better to one approach than the other.

Evidence from Wegovy trials

The STEP programme of clinical trials provides the main evidence for semaglutide’s effect on weight. In STEP-1, adults with overweight or obesity taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, compared with just 2.4% in the placebo group. Other STEP trials in different populations — including people with type 2 diabetes (STEP-2) and longer-term follow-up (STEP-5) — showed similarly strong outcomes. NICE used these results to support the approval of Wegovy in the UK, concluding that the medicine produces clinically meaningful and sustained weight loss when combined with lifestyle measures.

Evidence from Contrave/Mysimba trials

Contrave has also been studied extensively, though the results are more modest. Across pivotal trials, average weight loss ranged between 6% and 9% of body weight over one year. For example, the COR-I trial showed an average 6.1% reduction compared with 1.3% for placebo. Some participants achieved higher losses, but overall the effect size was smaller than that seen with semaglutide. Still, Contrave offered benefits for certain patients, particularly those struggling with food cravings or binge-eating tendencies, where its mechanism of action may be especially relevant.

Head-to-head comparisons

There have been no large head-to-head randomised controlled trials directly comparing Wegovy and Contrave. However, when results from separate trials are placed side by side, semaglutide consistently appears more effective. A typical person might expect to lose around 15% of their body weight with Wegovy over 68 weeks, versus 6–9% with Contrave over 56 weeks. These differences have shaped national guidance: NICE now prioritises Wegovy for use in specialist weight-management services, while Mysimba is available but with more limited uptake.

Side effects and tolerability

Effectiveness is only one part of the story. Wegovy and Contrave have different side-effect profiles that can influence individual experiences. Wegovy’s most common issues are gastrointestinal, particularly nausea, vomiting, or constipation during dose escalation. Contrave’s side effects often involve the nervous system, including headaches, insomnia, or increased anxiety, as well as nausea in some users. Some people tolerate one drug much better than the other, which is why prescribers stress that treatment must be individualised.

NHS perspective and access

In the UK, Wegovy is currently commissioned through NHS specialist services following NICE TA875, with strict criteria based on BMI and comorbidities. Mysimba is technically available as well, but in practice it has been less widely adopted, partly because of its more modest weight-loss effect and partly because prescribers tend to reserve it for those who cannot access or tolerate GLP-1 treatments. This reflects a broader trend in obesity medicine: GLP-1 receptor agonists like Wegovy and Mounjaro are now seen as leading therapies, while older agents play a secondary role.

Choosing between them

For most patients eligible for Wegovy, the evidence points to it being the more effective option. However, Contrave may still have a place, particularly for people who prefer an oral medicine over an injection or who have a history suggesting they may respond well to craving-control therapies. The decision is best made in consultation with a clinician, weighing up medical history, side-effect risks, access, and personal preference.

What this means in practice

The difference in efficiency between Wegovy and Contrave is clear: semaglutide generally produces greater and more sustained weight loss than the naltrexone/bupropion combination. While Contrave can still help some people, its effect size is smaller, and it is less widely used in the NHS today. For those who meet NICE criteria, Wegovy is usually the first choice, supported by robust trial evidence and clear commissioning pathways.