Semaglutide's impact on cardiovascular health expands beyond weight loss

Semaglutide, the popular anti-obesity medication originally developed to treat diabetes, continues to show cardiovascular benefits beyond weight loss, including reducing risk of death, reducing serious COVID-19 related events and improving heart failure (HF) symptoms, according to six new substudies published in JACC, the flagship journal of the American College of Cardiology. The research will be simultaneously published with presentations at the European Society of Cardiology Conference 2024 in London.

This portfolio of publications, derived from three major trials, significantly advances our understanding of the wide-ranging benefits of GLP-1 agonists, while also highlighting key questions that remain. These groundbreaking medications are poised to revolutionize cardiovascular care and could dramatically enhance cardiovascular health."

Harlan Krumholz, MD, FACC, JACC Editor-in-Chief and Harold H. Hines Jr Professor of Medicine, Yale University School of Medicine

Semaglutide improves CV outcomes regardless of sex, reduces COVID-19 related death in patients with obesity and CVD

In two new substudies of the SELECT Trial, which included people who had overweight or obesity according to BMI and had established cardiovascular disease but not diabetes, researchers looked at whether once weekly semaglutide (2.4mg) reduced rates of all-cause death, CV death and non-CV death, including death from COVID-19, and whether sex impacts the efficacy and safety of the drug

In the mortality substudy, rates of all-cause death, CV death and non-CV death were lower in people taking semaglutide vs. placebo. Semaglutide did not reduce incident COVID-19, but among those who developed COVID-19, those taking semaglutide had fewer COVID-19 related deaths.

In the sex differences substudy, researchers found females experienced fewer major adverse CV events compared to males, but semaglutide consistently reduced the risk of adverse CV outcomes regardless of sex.

Semaglutide reduces risk of HF events in people with diabetes and chronic kidney disease

Having both Type 2 diabetes and chronic kidney disease can increase the risk of HF and death compared to each condition alone. Semaglutide (1 mg) was previously shown to reduce the risk of major kidney disease events in this population, and in a new substudy from the FLOW trial, researchers looked at the effects of semaglutide on HF in this high-risk group. Once weekly semaglutide (1 mg) was shown to reduce the risk of time to first composite HF event (new onset or worsening HF leading to unscheduled hospital admission or urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death and HF events and CV death alone.

Semaglutide can improve HF outcomes by impacting pathophysiology of HFpEF patients

Semaglutide (2.4mg) improved obesity-related HF symptoms in people with inflammation and both with and without atrial fibrillation, plus improved cardiac structure and function, according to three new substudies from the STEP-HFpEF program.

Obesity can lead to inflammation in the heart, which can lead to the development and progression of obesity-related HFpEF. In the inflammation sub-study, researchers looked at patients in the STEP-HFpEF program with obesity-related HFpEF to determine the effect of semaglutide on HF symptoms and physical limitations in people with varying levels of inflammation at baseline. Inflammation was measured by levels of high-sensitivity C-reactive protein (CRP), which is a protein produced by the liver in response to inflammation or infection. Semaglutide improved HF-related symptoms, physical limitations and exercise function and reduced body weight in all categories of baseline CRP (<2, ≥2 to <10, and ≥10 mg/L), and improved inflammation regardless of baseline CRP or amount of weight loss.

Atrial fibrillation is common in people with HFpEF and is associated with worse outcomes, but less is known about the impact of semaglutide on obesity-related HFpEF outcomes in those with vs. without AFib. In the AFib sub-analysis, researchers examined the efficacy and safety of semaglutide in people with and without AFib within the STEP-HFpEF program and found that once weekly semaglutide (2.4mg) was associated with even greater improvements in HF-related symptoms and physical limitations in those with vs. without AFib, though improvements were seen in both groups.

Obesity can be associated with changes in the heart's structure, which can lead to the development and progression of HF. In the echocardiography sub-study, researchers found that once weekly semaglutide (2.4mg) improved multiple domains of cardiac structure and cardiac function, including improved left atrial volume, left ventricular diastolic function, and right ventricular size, compared with placebo.

"We do not yet fully understand how GLP1RA work, but these and other studies are showing that weight loss alone cannot completely account for the many kidney, metabolic, and kidney benefits that these agents provide," said Neha Pagidipati, MD, MPH, FACC, JACC associate editor and an associate professor of medicine and cardiometabolic disease prevention specialist at the Duke Clinical Research Institute.