select search filters
briefings
roundups & rapid reactions
before the headlines
Fiona fox's blog
Scientists react to MHRA approving semaglutide for heart problems.
Prof John Wilding, Professor of Medicine, Department of Cardiovascular and Metabolic Medicine, University of Liverpool, said:
“It is good news that the MHRA has approved semaglutide for prevention of further heart attacks and strokes in people living with obesity who already have cardiovascular disease. Obesity and overweight is an important risk factor for heart attacks, strokes and death from cardiovascular disease and the trial that supported this showed that treatment with semaglutide reduced the risk of people having one of these adverse outcomes by 20%. Semaglutide is already approved for treatment of obesity, but despite a favourable NICE appraisal since 2023, many people living with obesity in England and Wales are still unable to access this treatment due to funding restrictions and limited availability of NHS services for the treatment of obesity. It is hoped that this new widened indication will help funders of services to understand the benefits of treatment for people living with obesity, and provide appropriate support for clinical services to provide treatment.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“This decision is based on the robust results of a large (>17 thousand patient) around 4 years outcome trial in people living with prior heart disease or stroke or peripheral leg disease and high BMI. This is gold standard evidence. The safety findings were also reassuring and notably there were less severe adverse events in those prescribed semaglutide versus placebo, plus sustained weight loss over 4 years in the 5 out of 6 people who stayed on the medicine.
“The mechanism for benefits on major cardiovascular outcomes (the primary out in the trial) is likely largely due to the effects of the drug itself on slowing up the furring / blockage of blood vessels that supply heart or brain and so largely independent of weight loss actions. However, notably the achieved weight loss is hugely welcome for patients and adds potential for considerable other benefits as intentional weight loss can help improve quality of life (as appears in SELECT), and lower the risk of many other complications linked to obesity. We were asked to write an news and views article on the implications of this trial, entitled “What the SELECT trial of semaglutide means for clinicians” – and can be found here https://pubmed.ncbi.nlm.nih.gov/38796654/ Finally, hopefully other anti-obesity medicines currently being trials show similar patterns so that the pool of such medicines that can benefits many patients living with obesity and cardiovascular disease expands over time.”
Dr Martin Whyte, Associate Professor in Metabolic Medicine, University of Surrey, said:
“The MHRA decision has primarily arisen following clinical trial of semaglutide (SELECT trial) published last year. This took place in 17, 604 people aged 45 or over with cardiovascular disease (but not diabetes) and a BMI ≥27 kg/m2. This showed a 1.5% absolute risk reduction (from 8.0% to 6.5%) of composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. This is a 20% relative risk reduction. Overall, 67 people would need to be treated for 34 months to prevent one primary endpoint. These data were broadly in agreement with a 2016 study of the effects of semaglutide in people with type 2 diabetes and high cardiovascular risk.
“A later analysis of the SELECT data found that there was no difference in cardiovascular outcomes in those who did or did not achieve 5% weight loss after 20 weeks on semaglutide. This hints that weight loss per se may not a crucial factor, but any benefit may instead relate to benefits on blood pressure, glucose and body inflammation.
“Of interest, the trial participants tended to be older and with a greater pre-existing burden of cardiovascular disease than might be seen in a typical population receiving weight loss medication. Furthermore, approximately 1 in every 12 people treated with semaglutide had to discontinue the treatment due to adverse events or side effects. Therefore, the translatability of the trial data into real-world outcomes will need monitoring.”
Dr Simon Cork, Senior Lecturer in Physiology, Anglia Ruskin University (ARU), said:
“News that semaglutide has been approved for use specifically in people with established cardiovascular disease associated with obesity is welcomed.
“Importantly, recent research has shown that semaglutide was associated with a 20% reduction in major adverse cardiovascular events (such as heart attacks and stroke), which was independent of the amount of weight lost. This has important clinical implications because current guidelines state that patients should only continue with semaglutide if they achieve 5% body weight loss within 6 months. It remains to be seen whether these new approvals will retain this requirement in patients with established cardiovascular disease.”
Declared interests
Prof Wilding:
John Wilding reports consultancy / advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, AstraZeneca, Boehringer Ingelheim, Cytoki, Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, Shionogi & Ysopia; research grants for clinical trials from AstraZeneca and Novo Nordisk and personal honoraria / lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk and Rhythm.
He is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology and the Rank Prize Funds Nutrition Committee. He is national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network.
I was an investigator for the SELECT trial which was the 17600 patient RCT that provided the evidence for this new indication.
Prof Sattar: “I have consulted for several companies that make anti-obesity medicines including Eli Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Amgen, as well as other companies that market products in the cardiometabolic space.”
Dr Cork: “No COIS to declare.”
Dr Whyte: “I am a site PI at King’s College Hospital for the FOCUS study which is examining the effect of semaglutide on retinopathy. I am not a grant holder for this.”