What is the difference in weight loss mechanism between Wegovy and other appetite suppressants like Contrave?

Wegovy mimics the hormone GLP-1, acting on the brain to reduce appetite and slow digestion. Contrave (naltrexone/bupropion) affects brain reward and craving pathways, which can reduce emotional eating but doesn’t directly target satiety hormones.

How Wegovy works

Wegovy (semaglutide 2.4 mg weekly) is a GLP-1 receptor agonist. It mimics a natural gut hormone called GLP-1, which signals to the brain that you are full, slows down stomach emptying, and enhances insulin release when blood sugar rises. In practice, this leads to fewer cravings, smaller portions, and less frequent snacking. The STEP trials have shown that people using Wegovy can lose around 15% of their body weight over 68 weeks, with results sustained for up to two years in STEP-5.

How Contrave works

Contrave (known as Mysimba in the UK) is a combination of two older medicines: naltrexone, originally used in addiction treatment, and bupropion, an antidepressant and smoking cessation aid. Together, they act on the brain’s reward system, particularly the pathways linked to cravings and emotional eating. Instead of directly making people feel full, Contrave helps reduce the urge to eat for pleasure or in response to stress. Clinical studies such as the COR trials found average weight loss of 6–9% over a year, which is meaningful but less than what has been observed with semaglutide.

Why mechanisms matter

The contrast highlights why these medicines suit different people. Wegovy directly alters the biological satiety system, making it easier to stick to a lower-calorie diet without constant hunger. Contrave, on the other hand, is often most useful for people whose main challenge is emotional or reward-driven eating, since it dampens cravings rather than hunger itself. Both approaches can help, but the strength and consistency of results differ.

Safety and tolerability

The side effects also reflect the different mechanisms. Wegovy’s common issues are gastrointestinal — nausea, diarrhoea, or constipation — particularly during dose escalation. Contrave’s side effects are more neurological and cardiovascular, including headaches, insomnia, raised blood pressure, and sometimes anxiety. This is why Mysimba is not recommended for people with uncontrolled hypertension or certain psychiatric conditions.

NHS Guidance and use

In the UK, NICE recommends Wegovy within NHS specialist services for people with a BMI over 35 and weight-related conditions, or in some cases above 30. Mysimba is also licensed but used less frequently, partly because of its modest effectiveness and side-effect profile. It is more commonly accessed privately than through NHS programmes.

The full perspective

In terms of weight-loss mechanism, Wegovy and Contrave take very different routes: Wegovy suppresses appetite through the GLP-1 pathway, while Contrave works on brain reward circuits to reduce cravings. Both can support weight loss when combined with diet and exercise, but clinical trials show Wegovy produces larger and more consistent reductions in body weight, with added benefits for blood sugar and cardiovascular health.