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Glucagon-Like Peptide-1 Receptor Agonists and Risk for Gastroesophageal Reflux Disease in Patients With Type 2

Yunha Noh¹, Hui Yin², Oriana H Y Yu³

¹College of Pharmacy, Chonnam National University, Gwangju, South Korea (Y.N.).

Annals of Internal Medicine

|July 14, 2025

Abstract

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, which is a risk factor for gastroesophageal reflux disease (GERD). However, evidence linking these drugs to GERD is limited.

Objective:

To estimate 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.

Design:

Active-comparator new-user cohort study emulating a target trial.

Setting:

U.K. Clinical Practice Research Datalink.

Participants:

Adults aged 18 years or older with type 2 diabetes initiating GLP-1 RAs or SGLT-2 inhibitors between 1 January 2013 and 31 December 2021, with follow-up until 31 March 2022.

Measurements:

The primary outcome was incident GERD, and the secondary outcome was its complications. Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.

Results:

The study included 24 708 new users of GLP-1 RAs and 89 096 new users of SGLT-2 inhibitors. Over a median follow-up of 3.0 years, 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.

Limitation:

Residual confounding due to lack of information on dietary or lifestyle factors.

Conclusion:

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. Clinicians should be aware of this potential adverse effect to provide timely prevention and treatment strategies.

Primary Funding Source:

Canadian Institutes of Health Research.

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