How do the long-term health outcomes of Wegovy compare with those of Orlistat?

The SELECT trial showed semaglutide 2.4 mg (Wegovy) reduced the risk of major heart problems in people with overweight or obesity and cardiovascular disease. Orlistat, while useful for modest weight loss, has not shown the same scale of cardiovascular benefits in large outcome studies.

Two very different medicines

Wegovy and Orlistat are both prescribed for weight management, but they work in completely different ways. Wegovy (semaglutide) is a GLP-1 receptor agonist that reduces appetite, slows digestion, and helps regulate blood sugar. Orlistat works in the gut by blocking the absorption of dietary fat. These different mechanisms explain why their effects on long-term health outcomes are not the same.

Wegovy’s cardiovascular evidence

The SELECT trial, published in The New England Journal of Medicine and The Lancet, followed more than 17,000 adults with overweight or obesity and established cardiovascular disease. Participants taking Wegovy had a 20% lower risk of major cardiovascular events such as heart attack, stroke, or cardiovascular death compared with those on placebo. This is the first time a weight-loss medicine has been shown to improve hard cardiovascular outcomes on such a large scale.

Orlistat’s evidence base

Orlistat has been available for decades and has proven effective in producing modest weight loss, typically around 5–7% of body weight over a year. Some studies have shown that this reduction can improve blood pressure and cholesterol modestly. However, unlike semaglutide, Orlistat has not demonstrated clear benefits in reducing major cardiovascular events in large outcome trials. Its impact is largely limited to modest improvements in metabolic markers rather than long-term survival or heart health.

Side-effect profiles

The tolerability of these medicines also influences their long-term use. Orlistat commonly causes gastrointestinal side effects such as oily stools, bloating, and urgency, especially if dietary fat intake is not reduced. These can limit adherence. Wegovy also causes gastrointestinal side effects — mainly nausea and diarrhoea — but they are generally manageable with slow dose escalation. Importantly, the overall health benefits of Wegovy, including cardiovascular protection, outweigh these challenges for many people.

NHS guidance

NICE guidance now prioritises Wegovy as part of NHS specialist weight-management services because of its proven benefits for both weight loss and long-term health. Orlistat remains an option and is still prescribed in some cases, especially where GLP-1 therapies are unsuitable, but its effectiveness and long-term impact are more limited.

Why outcomes matter

When choosing a treatment, the goal is not only weight loss but also reducing the risk of future illness. The SELECT trial has set Wegovy apart by showing that significant weight loss combined with cardiovascular protection is possible with a single medicine. Orlistat can help some people lose weight, but its lack of evidence on heart outcomes means it plays a smaller role in long-term health strategies.

Key takeaways

Wegovy and Orlistat both help with weight management, but their long-term health outcomes are very different. Wegovy has demonstrated reduced risks of heart attack and stroke in large trials, while Orlistat has not shown this level of benefit. For people who meet eligibility criteria, Wegovy is now the stronger choice in NHS services for improving both weight and long-term health.