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  • Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study

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Oesophagus
Original research
Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study
  1. Benjamin Douglas Liu1,
  2. Sharon C Udemba1,
  3. Katherine Liang2,
  4. Yasir Tarabichi2,
  5. Hannah Hill3,
  6. Ronnie Fass4,
  7. Gengqing Song4
  1. 1 Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
  2. 2 Center for Clinical Informatics Research and Education, Metrohealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
  3. 3 Population Health and Equity Research Institute, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
  4. 4 Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
  1. Correspondence to Dr Gengqing Song, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA; songgavin2010{at}gmail.com

Abstract

Background Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications.

Aim To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications

Design We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs.

Results 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett’s without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett’s with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide.

Conclusion Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

  • gastroesophageal reflux disease
  • glucagen-like peptides
  • barrett's oesophagus
  • oesophageal strictures
  • erosive oesophagitis

Data availability statement

Data are available on reasonable request. All raw output data from TriNetX are available by contacting the corresponding author.

https://doi.org/10.1136/gutjnl-2023-329651

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    Data availability statement

    Data are available on reasonable request. All raw output data from TriNetX are available by contacting the corresponding author.

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    Footnotes

    • Contributors BDL: conceptualisation, investigation, data curation, data analysis, visualisation, drafting manuscript. SCU: data visualisation, drafting manuscript, editing manuscript. KL: methodology, data analysis, editing manuscript. YT: methodology, data analysis, editing manuscript. HH: methodology, validation, writing, editing manuscript. RF: editing manuscript. GS: conceptualisation, project supervision, writing, editing manuscript. GS is guarantor of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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