Semaglutide for obesity treatment

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. In this series of short videos, he explains the action of the drug and how it can be used to combat obesity effectively.

Managing obesity with semaglutide

Semaglutide is a synthetic analogue of glucagon-like peptide one (GLP-1). GLP-1 is a hormone produced in the distal part of the small intestine – the ileum – in response to the presence of food. It stimulates insulin release from the pancreas and it acts as a satiety hormone to signal fullness to the brain.

The STEP1 trial was a randomised, placebo-controlled trial of semaglutide for obesity in people who did not have diabetes. The results showed that participants achieved a 16 percent weight loss after one year compared with about two percent weight loss on placebo.  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”, says Professor Miras. The trial also showed that semaglutide 2.4 mg was well-tolerated with a favourable safety profile.

NICE appraisal of semaglutide for obesity

The GLP-1 agonists, first liraglutide (Saxenda) and now semaglutide, represent “a major revolution in the treatment of obesity”, says Professor Miras.

A single technology appraisal carried out by the National Institute for Health and Care Excellence (NICE) assessed the efficacy and cost-effectiveness of Wegovy (semaglutide) 2.4 milligrams for the treatment of obesity. It recommended that the medication should be available to people who have a body mass index over 35 kg/m² and at least one weight-related comorbidity.  It is also recommended for people with body mass indices of 30 to 35 kg/m² who also meet the criteria for referral to specialist weight management services.

The NICE guidance limits treatment to two years as semaglutide was not shown to be cost-effective for longer periods.  “That will create some more questions and some difficulties and challenges because we do not stop treatment for any other chronic disease and therefore there is no reason why we should do that for obesity”, says Professor Miras.

Obtaining and using semaglutide for obesity

Ideally, people seeking semaglutide treatment for obesity should be referred by their GP to a specialist weight management centre for treatment via the National Health Service. If this involves long delays some people may wish to seek a supply in the private sector. Professor Miras stresses the importance of having the support of a specialist weight management team in either situation.

Semaglutide will work on its own, without other measures, such as dietary changes, exercise or psychological interventions, but the combination can be additive or even synergistic.  The medication works is because it makes people change their diet. “The diet changes because of the drug ……. the vast majority of people will eat pretty much the same foods that they were eating before taking the medication but they would just eat less”, says Professor Miras. He also notes that the best way of enhancing the release of GLP-1 naturally is to eat high-protein meals.

Could semaglutide prevent cardiometabolic disease?

Obesity is a disease in which the mechanisms that normally control hunger and fullness are disrupted because of genetic mutations. The biological drivers that control body weight are very powerful. Approximately 70 percent of anyone’s body weight is determined by their genetic makeup and the other 30 percent depends on other environmental factors. It follows that treatment needs to be lifelong and not just for two years.

The SELECT trial is expected to show whether semaglutide has an impact on hard clinical outcomes. SELECT is a four-year trial, involving 17,000 participants with established cardiovascular disease, who were randomised to receive semaglutide 2.4 mg or placebo. The results are expected in Autumn 2023.

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

Read and watch the full series on our website or on YouTube.