GLP-1 Drugs Show Growing Promise for Afib Control

For patients with obesity and atrial fibrillation (Afib), GLP-1 receptor agonist drugs may be the weight loss approach that better addresses their arrhythmia, observational data suggested.

People who came out of catheter ablation and got bariatric surgery, as opposed to initiating GLP-1 drug therapy postablation, had significantly higher odds of Afib readmission at 2 years (36.4% vs 45.3%, HR 1.37, 95% CI 1.21-1.56), according to Rutvij Patel, MD, of Creighton University in Omaha, Nebraska, and colleagues.

Their analysis of a large trove of U.S. electronic medical records also showed other clinical endpoints favoring GLP-1 drugs over bariatric surgery:

• Heart failure (HF) readmission (HR 1.51, 95% CI 1.23-1.84)
• All-cause readmission (HR 1.55, 95% CI 1.32-1.82)
• All-cause mortality (HR 2.53, 95% CI 1.33-4.80)

“These findings were notable given that the GLP-1RA [receptor agonist] cohort had a higher baseline prevalence of diabetes, hypertension, HF, and chronic kidney disease,” study authors reported in JACC: Clinical Electrophysiology. “These findings highlight the potential role of GLP-1RAs as an adjunct in rhythm management strategies and support the need for prospective randomized trials.”

Afib is a common sustained arrhythmia that is strongly associated with obesity. Bariatric surgery has long been shown to be effective for long-term weight loss, but it has not reliably helped Afib recurrence in prior studies.

In recent years, many electrophysiologists are reportedly already using GLP-1 drugs instead in their clinical practice for weight loss in some patients. Observational studies on GLP-1 agonists had suggested potential reductions in arrhythmia recurrence, according to Patel’s group, with some theorizing that the mechanisms at work may involve reduced fat deposits around the heart or atrial remodeling reversal.

The present report arrives at a time when several modest-sized trials on weight loss and Afib just started or are about to start enrollment.

One that is still recruiting is the placebo-controlled TIRO-AF trial of tirzepatide (Zepbound) once weekly for control, management, symptom severity, and burden of Afib. Also on the horizon are METSAFE, a trial of Afib outcomes when obese patients are randomized to metabolic surgery versus nonsurgical controls who are given medications such as GLP-1 drugs, and WAIT, a Swedish trial testing semaglutide (Wegovy) given once weekly starting months before a first catheter ablation.

“To our knowledge, this study is the first direct comparison showing that GLP-1RAs are associated with superior postablation outcomes even among a more medically complex cohort. GLP-1RAs may confer benefits beyond weight reduction by improving atrial remodeling, reducing calcium-mediated arrhythmogenic triggers, and attenuating angiotensin II-driven fibrosis,” Patel and colleagues wrote.

Their retrospective cohort study relied on electronic health records from over 250 million patients across 142 U.S. healthcare facilities. Included were adults with a BMI ≥30 kg/m² who underwent Afib ablation from 2016 to 2025.

They were split into two groups: those who initiated GLP-1 receptor agonist therapy after ablation (n=4,501) and those who underwent bariatric surgery after ablation (n=1,681). Ultimately, propensity score matching was used to create comparable cohorts of 1,233 individuals each. Patients who received both therapies were excluded from the analysis.

Study authors assessed clinical outcomes past the initial 90-day blanking period.

Besides the aforementioned results, antiarrhythmic drug use was also higher for the bariatric surgery group (HR 1.19, 95% CI 1.03-1.38).

Meanwhile, there were no between-group differences in ischemic stroke, redo ablation, or cardioversion rates.

The study had usual limitations inherent to a retrospective, observational cohort study, including its potential for unmeasured confounding and reliance on data that were possibly miscoded. Furthermore, investigators lacked procedural details (e.g., ablation modality) and timing data between ablation and GLP-1 therapy initiation.

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