Manufacturer of semaglutide drugs Wegovy and Ozempic – Novo Nordisk – funded a study of 17,604 people that suggests semaglutide can lower the risk of heart-related deaths in certain cohorts of people with a BMI of 27 or more.
“There’s growing recognition that obesity and overweight are really metabolic diseases, and yet, effective therapies have been quite limited,” says cardiovascular researcher Michael Lincoff from Cleveland Clinic in Ohio.
“This marks the first pharmacologic intervention for overweight or obesity that’s been shown in a rigorous fashion to reduce the risk of cardiovascular events.”
Lindoff and an international team of researchers found that within the group who were given a weekly dose of semaglutide, there were almost 20 percent fewer heart disease-related deaths and non-fatal heart attacks or strokes, compared to the group who were given a placebo, over an average follow-up period of more than three years.
Broader research is needed to draw firm conclusions – the trial mostly comprised of men with an average age of 61, who had no diabetes diagnosis and had a history of cardiovascular disease. Nearly a quarter suffered from chronic heart failure, and more than three-quarters had previously suffered a heart attack.
Various heart conditions are more common in people with high BMIs and it is a good predictor of these problems in large studies of the general population, despite not being a reliable indicator of an individual’s health.
“The study takes on heightened significance when contextualized against the backdrop of high BMI contributing to a staggering 4 million global deaths in 2015, with cardiovascular diseases being the primary driver of over two-thirds of these fatalities,” metabolic neuroscientist Garron Dodd from the University of Melbourne, who wasn’t involved in the study, comments in an expert reaction.
“In a landscape where therapeutic options are basically non-existent, this research introduces a vital avenue for intervention.”
The double-blind study compared once-weekly injections of semaglutide (doses increasing over 16 weeks to a maximum of 2.4 mg) to a placebo. Over 90 percent of the participants were also on medication for a variety of cardiovascular risk factors, including high blood pressure, high cholesterol, and blood clotting.
The team looked at major adverse cardiovascular events, including cardiovascular death, non-fatal heart attack, and non-fatal stroke, to see if semaglutide protected the heart.
For that outcome, 8 percent of people who were given a placebo suffered from at least one of these major adverse cardiovascular events during the trial, compared to 6.5 percent of people who were given semaglutide.
Based on the small but significant difference of 1.5 percent between groups, this means that the relative risk was almost 20 percent lower for those given semaglutide.
“While the findings are exciting, caution must be exercised in interpreting them. The observed effects, while statistically significant, are relatively modest, emphasizing the need to avoid overinterpretation,” warns Dodd.
These reductions in cardiovascular event risk were comparable between sexes and between people of different ages, ethnicities, and BMIs at the start of the study.
Those taking semaglutide also showed greater reductions in their BMI and waist circumference, as well as heart rate, blood pressure, cholesterol, and an inflammatory biomarker, than those taking a placebo.
Semaglutide had some side effects, and more patients stopped taking it – 16.6 percent – compared to 8.2 percent for placebo. Most blamed gastrointestinal issues like nausea and diarrhea, symptoms that aren’t uncommon with this class of drugs.
The authors of the study note that further research is needed to determine how exactly semaglutide provides cardiovascular protection.
“The concept of treating obesity to reduce cardiovascular complications has been hampered by the lack of evidence that lifestyle or pharmacologic interventions for overweight or obesity improve cardiovascular outcomes,” says Lincoff.
“This study of semaglutide demonstrates the effectiveness of a new pathway to reduce the excess risk associated with obesity of important and potentially deadly cardiovascular complications.”
The study has been published in the New England Journal of Medicine.