Article Impact Level: HIGH Data Quality: STRONG Summary of Annals of Internal Medicine, ANNALS-24-03420. https://doi.org/10.7326/ANNALS-24-03420 Dr. Yunha Noh et al.
Points
- Researchers conducted an extensive cohort study to compare GERD risk in type 2 diabetes patients initiating either GLP-1 receptor agonists or SGLT-2 inhibitor medications.
- The study found that patients using GLP-1 RAs had a 27 percent higher relative risk of developing new-onset gastroesophageal reflux disease over a three-year follow-up period.
- For severe complications like Barrett esophagus, the relative risk was even greater, showing a 55 percent increase for patients taking GLP-1 receptor agonists versus the comparator drug.
- The risk of developing GERD complications was particularly pronounced in subgroups of patients who were smokers, had obesity, or had other existing gastric-related health conditions.
- These findings suggest clinicians should be aware of this potential adverse effect and monitor for GERD symptoms when prescribing GLP-1 receptor agonists for type 2 diabetes.
Summary
An extensive, active-comparator new-user cohort study was conducted to estimate the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus sodium–glucose cotransporter-2 (SGLT-2) inhibitors on the risk for gastroesophageal reflux disease (GERD). Using the U.K. Clinical Practice Research Datalink, researchers identified 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT-2 inhibitors with type 2 diabetes between 2013 and 2021. The study emulated a target trial design with a median follow-up of 3.0 years for the GLP-1 RA cohort and 2.7 years for the SGLT-2 inhibitor cohort.
Over the follow-up period, the overall incidence rate for GERD was 7.9 per 1,000 person-years. Compared with SGLT-2 inhibitor users, patients initiating GLP-1 RAs demonstrated a significantly higher risk of incident GERD, with a three-year risk ratio (RR) of 1.27 (95% CI, 1.14-1.42) and a risk difference (RD) of 0.7 per 100 patients. The risk was also elevated for GERD complications, which were observed in 138 patients and consisted of over 90% Barrett esophagus. The RR for complications was 1.55 (95% CI, 1.12-2.29), corresponding to an RD of 0.8 per 1,000 patients.
Secondary analyses indicated that the increased risk for GERD was consistent across most individual GLP-1 RA types, except lixisenatide. Furthermore, the risk for GERD complications was notably higher in subgroups of patients who were ever-smokers, had obesity, or had pre-existing gastric-related comorbidities. The study concluded that GLP-1 RAs are associated with a higher risk for GERD and its complications compared to SGLT-2 inhibitors in patients with type 2 diabetes, highlighting a potential adverse effect for clinicians to consider.
Link to the article: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03420
References Noh, Y., Yin, H., Yu, O. H. Y., Bitton, A., & Azoulay, L. (2025). Glucagon-like peptide-1 receptor agonists and risk for gastroesophageal reflux disease in patients with type 2 diabetes: A population-based cohort study. Annals of Internal Medicine, ANNALS-24-03420. https://doi.org/10.7326/ANNALS-24-03420
