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 approaches

Although both Wegovy and Contrave are prescribed for weight management, they work in completely different ways. Wegovy contains semaglutide, a GLP-1 receptor agonist that reduces appetite, slows digestion, and improves metabolic health. Contrave (Mysimba in the UK) is a combination of naltrexone and bupropion, two medicines originally used for addiction and depression. Together, they influence the brain’s reward system and reduce food cravings, particularly for highly palatable foods.

Evidence behind Wegovy

The strongest evidence for Wegovy comes from the STEP clinical programme. In STEP-1, published in The New England Journal of Medicine, participants using semaglutide 2.4 mg weekly alongside lifestyle support lost on average around 15% of their body weight over 68 weeks, compared with only 2–3% in the placebo group. The STEP-5 study extended follow-up to two years and showed that much of this weight loss could be sustained over time. These results have made Wegovy a benchmark for modern obesity treatment.

Evidence behind Contrave

Contrave has been tested in several large-scale trials, most notably the COR (Contrave Obesity Research) studies. These reported average weight loss of about 6–9% after one year, again in combination with reduced-calorie diets and physical activity. While this is a clear improvement over placebo, it is generally less than the reductions achieved with semaglutide in the STEP programme. For some people, especially those with strong food cravings or difficulties with emotional eating, Contrave can still be a helpful option.

What NICE says

In the UK, NICE has approved both treatments, but with different positioning. Wegovy is recommended as part of NHS specialist weight-management services for adults with a BMI over 35 and related conditions, or in some cases above 30. Mysimba (Contrave) is approved for use in adults with a BMI over 30, or over 27 with weight-related health issues, when lifestyle support alone hasn’t worked. However, its uptake within the NHS has been limited compared with Wegovy.

Side effects and tolerability

Wegovy and Contrave also differ in their side-effect profiles. Wegovy most often causes gastrointestinal issues such as nausea, diarrhoea, or constipation, particularly early in treatment. Contrave can cause headaches, insomnia, raised blood pressure, and nausea linked to bupropion’s stimulant effect. These differences mean tolerability varies widely between individuals. Doctors usually weigh both effectiveness and potential side effects when choosing between the two.

Practical considerations

Another difference is convenience. Wegovy is given once a week by injection pen, whereas Contrave is a daily oral tablet, starting with one dose and gradually increasing to two tablets twice daily. Some people prefer tablets, while others find a weekly injection easier to stick with. Both require commitment to diet and lifestyle changes for best results.

Why this detail matters

In direct comparison, Wegovy has shown greater average weight loss than Contrave in clinical studies. But effectiveness is not the only factor. Some people may respond better to Contrave, particularly if emotional or reward-driven eating is the main challenge. Others may prefer Wegovy because of its stronger clinical evidence and less frequent dosing. The “best” option depends on personal health needs, tolerability, and access through NHS or private care.