(A-309) Glucagon-like peptide-1 Receptor Agonists and the Risk of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), medications used to treat type 2 diabetes and obesity, are associated with delayed gastric emptying, a risk factor for gastroesophageal reflux disease (GERD). However, evidence linking these drugs to GERD is limited.

Objectives: To assess the effect of GLP-1 RAs compared with sodium–glucose cotransporter-2 (SGLT-2) inhibitors on the risk for GERD and its complications among patients with type 2 diabetes.

Methods: We conducted an active-comparator new-user cohort study using the UK Clinical Practice Research Datalink GOLD and Aurum databases. We assembled a cohort of patients aged ≥18 years with type 2 diabetes who were newly prescribed GLP-1 RAs or SGLT-2 inhibitors between January 1, 2013, and December 31, 2021, with follow-up until March 29, 2022. The primary outcome was a diagnosis of incident GERD, and the secondary outcome was complications of GERD, defined as a composite of Barrett’s esophagus, esophageal stricture, and erosion or ulceration of esophagitis. Based on an intention-to-treat exposure definition. we estimated risks (cumulative incidences), risk differences (RDs), and risk ratios (RRs) at 1, 2, and 3 years of follow-up (3-year as primary), with 95% confidence intervals (CIs), and weighted using propensity score fine stratification to control for confounding.

Results: The study included 24 708 new users of GLP-1 RAs and 89 096 new users of SGLT-2 inhibitors, with a mean age of 56.7 years (SD 12.4), 54.6% male, and a median follow-up of 3.0 year. During follow-up, there were 1954 GERD events, with an incidence rate of 7.9 (95% CI, 7.5 to 8.2) per 1000 person-years. At 3 years of follow-up, the RRs were 1.27 (95% CI, 1.14 to 1.42) for GERD, with an RD of 0.7 per 100 patients, and 1.55 (95% CI, 1.12 to 2.29) for its complications, with an RD of 0.8 per 1000 patients, among GLP-1 RA users compared with SGLT-2 inhibitor users. Similar effects were observed at 1 and 2 years of follow-up. In secondary analyses, most GLP-1 RAs (both short- and long-acting agents) increased risk for GERD, and its complications were elevated among ever-smokers, patients with obesity, and patients with comorbidities associated with gastric motility.

Conclusions: The estimated effect of GLP-1 RAs compared with SGLT-2 inhibitors suggested a higher risk for GERD and its complications in patients with type 2 diabetes. While our findings need to be corroborated in other studies, clinicians and patients should be aware of this potential adverse effect to provide timely prevention and treatment strategies.