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Semaglutide cuts risk of MACE in overweight or obese adults, trial results suggest

Semaglutide has been found to reduce the risk of major adverse cardiovascular events (MACE) by 20% in overweight or obese adults, its manufacturer Novo Nordisk has claimed.

According to headline results from the SELECT study, the anti-diabetic drug semaglutide was able to cut the risk of overweight or obesity experiencing a MACE by 20% compared to placebo.

This randomised, double-blind, placebo-controlled trial, the results of which are yet to be published in a peer-reviewed journal, was designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo, as an adjunct to standard of care, for the prevention of MACE, in overweight or obesity with no prior history of diabetes.

The primary endpoint of the study was defined as the composite outcome of the first occurrence of MACE defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.

Commenting on the findings, Martin Holst Lange, executive vice president for development at Novo Nordisk, said: ‘People living with obesity have an increased risk of cardiovascular disease but, to date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke or cardiovascular death. Therefore, we are very excited about the results from SELECT showing that semaglutide 2.4 mg reduces the risk of cardiovascular events.‘

He added: ‘SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.‘

Semaglutide and MACE

SELECT enrolled 17,604 adults across 41 countries at more than 800 investigator sites and was initiated in 2018.

All participants had pre-existing cardiovascular disease, including a prior myocardial infarction (76.3%) or stroke (23.3%). In addition, enrolled participants were aged ≥45 years with a body mass index (BMI) ≥27 kg/m2.

In total 1,270 first MACEs accrued. The trial achieved its primary objective by demonstrating a statistically significant and superior reduction in MACE of 20% for people treated with semaglutide 2.4 mg compared to placebo.

In the trial, semaglutide 2.4mg appeared to have a safe and well-tolerated profile in line with previous semaglutide 2.4mg trials.

Naveed Sattar, professor of metabolic medicine at the University of Glasgow, said: ‘More details are needed on the trials to give it proper consideration, including examination of safety aspects, but even here the top line report also sounded optimistic. 

‘The one thing to caution is we do not know to what extent the weight loss effects of semaglutide as opposed to its other direct effects on blood vessels or the heart, account for the 20% reduction in cardiovascular events, and more data are needed to try to work this out.

‘For now, however, this is a good result for patients, especially as progressively more are living with obesity and cardiovascular disease.‘

Novo Nordisk expects to file for regulatory approvals of a label indication expansion for semaglutide 2.4 mg in the US and the EU later in 2023. The detailed results from SELECT will also be presented at a scientific conference later in the year.

In March, NICE recommended Wegovy for use as part of a patient’s treatment for obesity in an NHS specialist weight management service and with the support of a multi-disciplinary team.

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