A large UK study has found that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may raise the risk of gastroesophageal reflux disease (GERD) and related complications.
Researchers analyzed data from the Clinical Practice Research Datalink, which includes medical records from more than 60 million patients. They identified 24,708 adults with type 2 diabetes who began treatment with a GLP-1 RA between 2013 and 2021 and compared them with 89,096 patients who started sodium–glucose cotransporter-2 (SGLT-2) inhibitors. Patients with prior GERD, reflux-like symptoms, or related conditions were excluded to reduce bias.
Using a target trial emulation framework and propensity score weighting to balance comorbidities, researchers tracked outcomes over a median of three years. The primary endpoint was a new diagnosis of GERD; secondary outcomes included complications such as Barrett esophagus, esophageal strictures, or erosive esophagitis, noted Laurent Azoulay, PhD, (McGill University, Montreal, Quebec, Canada) and colleagues.
Researchers found a 27% higher relative risk of GERD among GLP-1 RA users compared with those on SGLT-2 inhibitors (risk ratio [RR], 1.27; 95% CI, 1.14–1.42). That translated to about 0.7 additional GERD cases per 100 patients over three years. The risk of GERD-related complications was greater (RR, 1.55; 95% CI, 1.12–2.29), although the absolute increase was small, at 0.8 per 1,000 patients.
The findings build on earlier safety concerns about GLP-1 RAs, which are known to slow gastric emptying, leading to nausea, vomiting, and in rare cases, gastroparesis. Because delayed gastric emptying can worsen reflux, the association with GERD has been suspected but not well quantified until now.
"These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD. Although our findings need to be corroborated in other studies, clinicians and patients should be aware of a possible adverse effect of GLP-1 RAs on GERD," wrote Azoulay and fellow authors.
They noted that unmeasured lifestyle and dietary factors may have influenced results, but concluded that clinicians should remain alert to reflux symptoms in patients starting GLP-1 RAs. Early recognition and treatment of GERD could help prevent long-term esophageal complications, especially as use of these drugs continues to expand for diabetes and obesity management.
Full author disclosures are available in the link below.
Source: Annals of Internal Medicine
