Meta-analyses of global GLP-1 RA studies highlight safety and new potential role of GLP-1 RAs

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use in patients with diabetes or heart diseases is not associated with increased risk of optic nerve or vision-threatening events, and plays a role in improving the long-term success rate of curative catheter ablation for atrial fibrillation (AF) in cardiac patients with obesity, researchers from the University of Hong Kong (HKU) have found.

One of the meta-analyses performed by the team evaluated data from 20 global randomized control trials (RCTs), which included 83,288 patients with diabetes and heart disease, representing the largest sample size examined in this field to date. Studies which investigated use of GLP-1 RAs in type 2 diabetes (T2D)/cardiometabolic disease populations and reported optic nerve or vision-related adverse events (AEs) were assessed. The primary outcome was a composite of optic nerve and/or vision-threatening serious AEs, including ischaemic optic neuropathy (ION), ocular ischaemic syndrome, papilledema, blindness, blurred vision, visual impairment, and reduced visual acuity. [Diabetes Care 2026;doi:10.2337/dc25-1929]

About three-quarters (76.4 percent) of included patients had T2D. Over a mean follow-up of 2.97 years (estimated cumulative exposure of 240,334 patient-years), GLP-1 RA use was not found to be associated with an increased risk of the primary endpoint (odds ratio [OR], 1.20; 95 percent confidence interval [Cl], 0.73–1.97).

The researchers also examined how GLP‑1 RAs compare with other weight‑loss interventions (including lifestyle modification, cardiovascular [CV] risk factor optimization, and bariatric surgery) in preventing AF recurrence after catheter ablation, as obesity is a feature of the cardiometabolic disease spectrum, in which AF is a common comorbidity, and obesity may diminish the success of AF ablation. [Eurospace 2025;27:i565-i567]

Their meta-analysis evaluated data from two RCTs and 11 cohort studies (n=5,364). Results showed a 6.3 percent relative risk reduction in AF recurrence for each 1 percent absolute decrease in body weight achieved, regardless of the choice of perioperative weight loss intervention. In subgroup analyses, bariatric surgery was associated with significantly reduced risk of AF recurrence, while GLP-1 RAs showed a trend towards protection with borderline statistical significance.

The researchers thus noted that for cardiac patients with obesity, improving weight control through a holistic approach such as adopting a healthier lifestyle and using adjunct clinical interventions together with GLP‑1 RAs may improve the long‑term success rate of catheter ablation for AF. They emphasized that optimal treatment outcomes depend on comprehensive CV risk management rather than reliance on medication alone.

Growing evidence that GLP‑1 RAs improve cardiometabolic risk profiles is broadening their use beyond glycaemic control and weight management. However, some observational studies have raised concerns about a possible link between GLP‑1 RAs and ION, a vision‑threatening condition with limited treatment options. Although these findings were inconsistent, the concerns prompted the researchers to further evaluate the safety and therapeutic potential of GLP‑1 RAs. [Diabetes Care 2026;doi:10.2337/dc25-1929]

“Our meta-analysis of clinical trial data provides important evidence regarding both the safety profile and novel use of GLP-1 RAs in CV patients, enabling a more comprehensive evaluation of the potential risks and benefits of these medications,” said lead investigator, Dr Will Yap-Hang Chan of the Department of Medicine, HKU. “The possibility of rare adverse complications, however, cannot be ruled out. Clinicians should therefore always exercise careful judgment, assess each patient holistically, and avoid focusing solely on potential benefits while overlooking associated risks.”