Wegovy lowers CVD deaths in non-diabetics

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The weight-loss drug cut major cardiovascular events by 20% in overweight people with heart disease.

Wegovy reduces the risk of heart attack, stroke and death over several years in overweight and obese patients without diabetes, according to a new large study in NEJM.

This is the first clinical trial to show semaglutide (Novo Nordisk) can reduce cardiovascular events in non-diabetics.

“This study’s findings carry significant implications, especially considering the alarming projection that more than half the global population will grapple with overweight or obesity by 2035,” Associate Professor Garron Dodd, metabolic neuroscientist at the University of Melbourne, said in a statement.

“In a landscape where therapeutic options are basically non-existent, this research introduces a vital avenue for intervention.”

The manufacturer-funded trial included 18,000 patients across 41 countries who had preexisting cardiovascular disease such as a history of heart attack, stroke or peripheral artery disease.

All participants were 45 or older with no history of diabetes and had a BMI in the overweight or obese range (27 or greater).

Participants were randomly assigned to weekly 2.4mg injections of either semaglutide or placebo, alongside standard treatment for their cardiovascular disease such as beta blockers and cholesterol lowering medication.

Over the three years of treatment and five-year total follow up, 8% of the control group experienced major cardiovascular events compared with 6.5% of those taking the GLP-1 agonist.

This 20% risk reduction in heart attacks, stroke and death was similar across gender, ethnicity, age and baseline bodyweight.

Twice the number of participants stopped semaglutide treatment due to gastrointestinal side effects such as nausea and diarrhea compared with the placebo group.

They also experienced a slightly higher rate of gallbladder disorders, at a rate of 2.8% compared with 2.3% in the placebo group.

But semaglutide was not associated with a higher risk of gastrointestinal disorders, pancreatitis, kidney injury or psychiatric disorders.

The researchers pointed to changes in biomarkers, such as improved blood glucose levels, blood pressure, cholesterol and inflammation as possible drivers of the benefits.

“For perspective, the observed decrease of 3.3mmHg in systolic blood pressure in this trial is greater than the decrease of 2mmHg predicted by a meta-analysis to yield a 7% reduction in vascular mortality, and the 37.8-percentage-point decrease in the high-sensitivity C-reactive protein level with semaglutide in this trial is similar to that reported with statins,” the authors wrote.

“These changes in cardiovascular biomarkers are notable for having been achieved on a background of high rates of use of statins, antihypertensive agents, and other evidence-based medications for atherosclerotic disease.”

Professor Dodd was cautious about interpreting the results.

“The mechanism through which semaglutide protects against cardiovascular-related death remains unclear, with questions arising about whether the observed benefits are solely attributed to weight loss, given the 8.5% greater reduction in body weight in the semaglutide-treated group,” he said.

“Furthermore, the study’s focus on patients with mild or stage 1 obesity [average BMI around 33] prompts scrutiny regarding the potential applicability of these effects in severely obese patients, who arguably face the highest risk of cardiovascular death. Notably, the study’s authors and funders hail from Novo Nordisk, the pharmaceutical giant behind the development and global trade of semaglutide.”

NEJM 2023, online 11 November

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