Obesity: Appetite drug could mark 'new era' in tackling condition
Some of the people on the 15-month trial lost more than a fifth of their body weight.
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The drug works by hijacking the body's appetite levels and mimicking a hormone - called GLP1 - that is released after eating a filling meal.
The trial gave some people the drug and others a dummy injection, while both groups were given the lifestyle advice.
The results, published in the New England Journal of Medicine, showed people lost an average of 15kg on semaglutide compared with 2.6kg without.
However, 32% of people lost a fifth of their body weight with the drug, compared with fewer than 2% on the dummy treatment.
Prof Rachel Batterham, from UCL and one of the UK researchers, told the BBC News website: "This is a game-changer in the amount of weight loss it causes.
"I have spent the last 20 years doing obesity research, up until now we've not had an effective treatment for obesity apart from bariatric surgery."
Prof Sir Stephen O'Rahilly, from the University of Cambridge, said: "The amount of weight loss achieved is greater than that seen with any licensed anti-obesity drug.
"This is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side-effects."
Dr Duane Mellor, a dietician and from Aston Medical School, said: "It is useful to have a potential option to help people lose weight, however we need to acknowledge that weight loss will still need lifestyle change, and that any medication or change in lifestyle can bring potential risks and side-effects.
"So, it is always wise to speak to a health professional before trying to lose weight."