TOPLINE:

Patients with heart failure with reduced ejection fraction (HFrEF) and implanted cardiac devices who used GLP-1 receptor agonists had higher heart rates, greater number of nonsustained ventricular tachycardia events, and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) than those who did not use the drugs.

METHODOLOGY:

• This retrospective analysis from a Canadian health center evaluated whether the use of GLP-1 receptor agonists affected heart rate and device-related measures in 106 patients with HFrEF and implanted cardiac devices (mean age, 66 years; 81% men; mean BMI, 31.4).
• Investigators compared outcomes in 53 patients who initiated GLP-1 therapy after device implantation with those in 53 patients who did not use the drugs between January 2023 and June 2024.
• The primary outcome was the difference in heart rate between GLP-1 receptor agonist users and nonusers. Secondary outcomes were arrhythmic events, changes in BMI, and laboratory biomarkers.
• Patients were followed up for up to 1 year, and device-related outcomes were monitored at four timepoints.

TAKEAWAY:

• Heart rate was 7 beats per minute higher in GLP-1 receptor agonist users than in nonusers (P < .01), with the mean difference reaching up to 13 beats per minute in the final phase of evaluation.
• GLP-1 receptor agonist users vs nonusers had a more nonsustained ventricular tachycardia events (3372 vs 399; P < .01) and total shocks or antitachycardia pacing therapies (33 vs 3; P = .01).
• Investigators observed more events of ventricular tachycardia or fibrillation among GLP-1 receptor agonist users vs nonusers, although the difference was statistically nonsignificant (13 vs 2; P = .07).
• GLP-1 receptor agonist use was associated with a 0.45-log units increase in NT-proBNP levels vs nonuse (P = .007). However, GLP-1 receptor agonist users had greater reductions in BMI and A1c levels (P < .05 for both). The number of HF events or all-cause hospitalizations did not differ between the groups.

IN PRACTICE:

“Despite the obvious appeal of using potent new antiobesity medications to treat all forms of obesity-associated HF, data such as those in this study by Marques et al, should persuade us to perform well designed large randomized clinical trials testing the strategy in patients with HFrEF before embracing this approach,” experts wrote in an editorial comment accompanying the article.

“Some patients with severe HF decompensations or ventricular arrhythmias may need to permanently discontinue the GLP-1 receptor agonist therapy and pursue alternate type 2 diabetes or obesity treatment strategies,” two experts wrote in a Leading Edge commentary.

SOURCE:

This study was led by Pedro Marques, MD, MSc, of McGill University Health Centre in Montréal, Québec, Canada. It was published online on September 23, 2025, in JACC: Heart Failure.

LIMITATIONS:

This study was retrospective and did not establish that GLP-1 receptor agonists caused the observed effects. The sample size was inadequate to detect significant differences in clinical events. The groups were not completely balanced at baseline, although analyses were adjusted for the differences.

DISCLOSURES:

No funding source was explicitly mentioned for this study. Several authors reported receiving salary support, consulting and speaker fees, personal fees, honoraria, or research grants from and having other financial ties with various organizations and pharmaceutical, healthcare, and biotechnology companies, including the Canadian Institute of Health Research, Janssen, Lilly, and Medtronic. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.