Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis

Sun, Yan; Veccia, Donovan; Liu, Benjamin Douglas Xun; Tse, William; Fass, Ronnie; Song, Gengqing

doi:10.3390/diagnostics15172264

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Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis

by

Yan Sun

^1,†,

Donovan Veccia

^2,†,

Benjamin Douglas Xun Liu

¹,

William Tse

³,

Ronnie Fass

² and

Gengqing Song

^2,*

¹

Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA

²

Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA

³

Division of Hematology and Oncology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Diagnostics 2025, 15(17), 2264; https://doi.org/10.3390/diagnostics15172264 (registering DOI)

Submission received: 18 July 2025 / Revised: 29 August 2025 / Accepted: 29 August 2025 / Published: 7 September 2025

(This article belongs to the Special Issue Advances in Diagnosis of Digestive Diseases)

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Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively manage type 2 diabetes mellitus (T2DM) but may impair gastrointestinal motility, increasing the risk of small intestinal bacterial overgrowth (SIBO). Diagnostic evaluation of SIBO commonly involves breath testing and clinical assessment. This study aimed to assess the association between GLP-1 RAs or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are associated with incident SIBO. Methods: We conducted a retrospective cohort study using the TriNetX global database, identifying adult T2DM patients initiating GLP-1 RA or dual GLP-1/GIP RA therapy versus other second-line T2DM agents (OSLT2DM) from 1 January 2006 to 2 December 2024. Patients with major abdominal surgery, connective tissue disorders, gastroparesis, or other high-risk conditions for SIBO were excluded. 1:1 Propensity score matching was applied. Short-term (<1 year) and long-term (up to 5 years) risks were evaluated with Kaplan–Meier curves and univariable Cox models. Results: After matching, 216,173 patients per cohort were analyzed. Short-term analysis demonstrated a higher incidence of diagnostically confirmed SIBO in patients treated with GLP-1 RA/GIP (0.177 per 1000 patient-years) compared to OSLT2DM (0.083 per 1000 patient-years; HR 2.14, 95% CI 1.13–4.07; p = 0.0491). Long-term analysis indicated a non-significant trend toward increased risk in the GLP-1 RA/GIP group (HR 2.02, 95% CI 0.98–4.12), though Kaplan–Meier analysis revealed a sustained divergence (p = 0.017). Conclusions: GLP-1 RA and dual GLP-1/GIP RA therapy are associated with increased short-term SIBO risk. Symptom-driven SIBO breath-test evaluation may be warranted in patients initiating these agents.

Keywords: GLP-1 receptor agonists; small intestinal bacterial overgrowth; diagnostic evaluation; breath test; SIBO; diabetes mellitus; gastrointestinal motility; dual GLP-1/GIP receptor agonists; Trinetx database

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MDPI and ACS Style

Sun, Y.; Veccia, D.; Liu, B.D.X.; Tse, W.; Fass, R.; Song, G. Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis. Diagnostics 2025, 15, 2264. https://doi.org/10.3390/diagnostics15172264

AMA Style

Sun Y, Veccia D, Liu BDX, Tse W, Fass R, Song G. Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis. Diagnostics. 2025; 15(17):2264. https://doi.org/10.3390/diagnostics15172264

Chicago/Turabian Style

Sun, Yan, Donovan Veccia, Benjamin Douglas Xun Liu, William Tse, Ronnie Fass, and Gengqing Song. 2025. "Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis" Diagnostics 15, no. 17: 2264. https://doi.org/10.3390/diagnostics15172264

APA Style

Sun, Y., Veccia, D., Liu, B. D. X., Tse, W., Fass, R., & Song, G. (2025). Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis. Diagnostics, 15(17), 2264. https://doi.org/10.3390/diagnostics15172264

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Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis

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