Anti-obesity drugs, lifestyle interventions show cardiovascular benefits beyond weight loss

Popular anti-obesity drugs continue to show cardiovascular benefits beyond weight loss, according to several new papers published in JACC that are being simultaneously presented at the American Heart Association’s 2024 Scientific Sessions. JACC is publishing two secondary analyses on the impact of GLP-1 medications in improving cardiac structure and function in heart failure patients and cardiovascular outcomes in those who previously had cardiac bypass surgery, plus a new analysis of a lifestyle intervention trial showing that cardiac risk biomarkers change with weight loss.

“These studies reinforce the potential of GLP-1-based therapies not only to aid in weight loss but also to transform cardiac health, offering hope for patients living with obesity and cardiovascular disease,” said Harlan M. Krumholz, MD, SM, editor-in-chief of JACC and the Harold H. Hines Jr. Professor of Medicine at Yale University School of Medicine. “As the science evolves, we are achieving a deeper understanding of how weight loss, and treatment with these medications, can improve outcomes across diverse patient populations with obesity.”

Tirzepatide decreases heart size to improve cardiac structure, function

In a secondary analysis of the SUMMIT trial, researchers looked at the effect of the combined GLP-1 and GIP receptor agonist tirzepatide on cardiac structure and function in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Tirzepatide has already been FDA approved for weight loss. Researchers looked at 106 patients from the main SUMMIT study who underwent imaging to analyze left ventricular (LV) mass and epicardial adipose tissue (EAT) at baseline and 52 weeks.

Results showed that tirzepatide decreased LV mass by 11 g and decreased paracardiac adipose tissue by 45 ml in the treated group compared to the placebo group. EAT decreased in both groups. According to researchers, the decrease in heart size may be a contributing factor in the reduction in heart failure events seen in the main SUMMIT trial, which was also presented at AHA 2024 Scientific Sessions.

Semaglutide improves cardiac outcomes in patients after cardiac bypass surgery

In a secondary analysis of the SELECT trial, patients who have already had cardiac bypass surgery and are living with obesity or overweight but not diabetes were randomized to receive once-weekly semaglutide or placebo to determine if it improved cardiac outcomes. This patient population is at a higher risk of persistent ischemic events, heart failure and death, but there is little data on how to improve secondary outcomes in these patients after heart surgery.

In the analysis, 2,057 participants had a history of CABG and 15,547 did not. Those with CABG were older (65 years old vs. 61 years old), 84% were male vs. 70%, 2.1% were Black vs. 4%, and they had a lower BMI (31.9 kg/m² vs. 32.1 kg/m²). Semaglutide led to a consistent reduction in major adverse cardiovascular events in both groups, but the absolute risk reduction with semaglutide was greater in those with a history of CABG (2.3% vs. 1%). Semaglutide was also shown to reduce the incidence of diabetes in the CABG group.

Weight loss via lifestyle intervention can change cardiac biomarkers

A secondary analysis of the LookAHEAD trial showed that lifestyle interventions targeting weight loss for type 2 diabetes patients led to a change in biomarkers associated with higher risk of cardiovascular disease and heart failure. Cardiac biomarkers are measured to determine if people with type 2 diabetes are at elevated risk for developing heart failure. It is known that weight loss and exercise can reduce risk for cardiovascular disease, but less is known about changes in biomarkers.

Researchers found that lifestyle interventions led to sustained reductions in high-sensitivity cardiac troponin T (hs-cTnT) at one and four years follow-up, and a rise in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at one year attenuated at four years. Changes in these biomarkers are clinically relevant for patients with Type 2 diabetes, as the researchers found that patients with elevated NT-proBNP and hscTnT were at greater risk of future ASCVD, and that patients with elevated NT-proBNP were also at greater risk of developing HF.