Semaglutide – a game-changer in obesity management

Alex Miras is Professor of Endocrinology at the University of Ulster, UK and is an expert in obesity management and research. In 2021 a trial of semaglutide for obesity ”changed our expectations of obesity treatments”, he says. IMI spoke to him to find out more about the semaglutide (Wegovy, Ozempic) and how it can be used to combat obesity effectively.

Semaglutide is a synthetic analogue of glucagon-like peptide one (GLP-1). It is a hormone produced in the intestine when we eat. “It does two things. It makes our pancreas produce insulin to reduce our blood glucose but it also signals to the brain fullness – so it is a satiety hormone”, explains Professor Miras. Experience of GLP-1 agonists over the past 16 years in the treatment of diabetes has shown that people not only see reduced glucose levels but also weight loss. The satiety-inducing effect therefore underpins the use of GLP-1 receptor analogues for the treatment of the disease of obesity.

Liraglutide, another GLP-1 receptor agonist, was launched some time ago and it differs from semaglutide in several respects. The use of this group of drugs started with products that had to be injected twice a day. Liraglutide was approved for obesity with the brand name of Saxenda, and this is injected once a day whereas semaglutide is injected once a week.

“What we know is that while this development has been taking place, the efficacy of the medications has been increasing.  So, liraglutide (Saxenda) …… can cause approximately eight percent weight loss at three milligram dose, …… whereas Wegovy, which is semaglutide 2.4 milligrams can cause almost 16 percent weight loss at one year”, says Professor Miras.

The STEP1 trial was a randomised, placebo-controlled trial of semaglutide for obesity in people who did not have diabetes.  “What they found was that the total percent weight loss at approximately a year or so after initiation of treatment was 16 with the medication is about as opposed to about two percent or so with placebo”, he explains.  At the time of publication this was “the most effective medication available for weight loss …….. it changed our thinking about obesity, it changed our expectations of obesity treatments”, he adds.

Moreover, it also showed that semaglutide 2.4 mg was well-tolerated with a favourable safety profile.  Common side-effects are gastro-intestinal including nausea, diarrhoea or constipation but these disappear with time in most people.  “Less than 10 or even less than five percent of people … have to discontinue treatment because of side effects”, says Professor Miras. There is also a small risk of developing gallstones and cholecystitis, but these are rare, he comments.

Disclosures:
Grants/Research Support: Fractyl, Novo Nordisk, Randox.
Other Financial or Material Support/Honoraria: Novo Nordisk, GI Dynamics, AstraZeneca, Boehringer Ingelheim, Currax Pharmaceuticals

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