GLP-1 use may prevent recurrent arrhythmia events for patients with diabetes, obesity
Key takeaways:
- Diabetes management-dose GLP-1 use reduces recurrent arrhythmic events for patients with atrial fibrillation and obesity.
- The highest benefit was observed for those with severe obesity.
GLP-1 use significantly lowered risk for atrial fibrillation-related events for patients with diabetes, AF and obesity, with particular benefit observed for those with severe obesity, a speaker reported.
The results of the multicenter TRANSFORM-AF study were presented at Heart Rhythm 2025.
“The whole premise of this study is that the residual risk of AF, even post-ablation, is not trivial, and it’s quite significant. Almost one-third of them having recurrence within a year. One plausible reason for this high residual risk is suboptimally managed cardiometabolic risk factors, and obesity is a predominant driver in the Western population,” Varun Sundaram, MD, PhD, MSc, section chief of advanced heart failure at the Louis Stokes Cleveland VA Medical Center, University Hospitals Harrington Heart & Vascular Institute and associate professor of medicine at Case Western Reserve University, said during a discussion after the presentation. “That was the premise of the study, where it’s a pharmacoepidemiologic study across the entire Veterans Affairs health system, where we investigated the relationship between GLP-1 receptor analog use and the burden of atrial fibrillation in patients with preexisting AF and obesity.”
TRANSFORM-AF included 2,510 patients with diabetes, AF and obesity across 170 VA hospitals. All patients were assigned a GLP-1 receptor agonist, dipeptidyl-peptidase IV (DPP-IV) inhibitor or sulfonylurea.
The primary composite outcome was major AF-related events, including hospitalizations for AF, cardioversions and ablation procedures in the GLP-1 groups compared with the DPP-IV inhibitor or sulfonylurea comparator group.
Patients assigned a GLP-1 receptor agonist were more often older with a higher burden of comorbidities compared with those treated with DPP-IV inhibition or sulfonylurea.
During a median follow-up of 3 years, GLP-1 use was associated with an approximately 13% lower risk for major secondary AF-related events compared with DPP-IV inhibition or sulfonylurea use for patients with diabetes, AF and obesity (HR = 0.87; 95% CI, 0.68-0.96; P = .03).
When the researchers added mortality as a competing risk, they observed an approximately 15% reduced risk for secondary AF-related events with GLP-1 use compared with DPP-IV inhibition or sulfonylurea use (HR = 0.85; 95% CI, 0.61-1.03).
The researchers reported observing greatest benefit among patients with BMI more than 40 kg/m2.
Weight loss from GLP-1 use in the TRANSFORM trial was reported to be modest, with an approximately 4% greater reduction vs. the comparator group.
“In the absence of randomization, we should view the findings as hypothesis-generating. ... The feasibility of a randomized trial in the way all of us would want would be quite challenging, as we’ll have to randomize patients who are obese with AF to a control group with no GLP-1 receptor agonists,” Sundaram said during the discussion. “We should consider managing obesity along with atrial fibrillation through ablations and drugs ... [and] use obesity as an indication to consider using a GLP-1 receptor agonist along with conventional therapy for AF.”
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Selvaganesan P, et al. Late-breaking clinical trials and science: Clinical trial updates and registries. Presented at: Heart Rhythm 2025; April 24-27, 2025; San Diego.