{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:29:55Z","timestamp":1787837395067,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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 (&lt;1 year) and long-term (up to 5 years) risks were evaluated with Kaplan\u2013Meier 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\u20134.07; 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\u20134.12), though Kaplan\u2013Meier 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.<\/jats:p>","DOI":"10.3390\/diagnostics15172264","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:06:32Z","timestamp":1757318792000},"page":"2264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.3390","volume":"15","author":[{"given":"Yan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donovan","family":"Veccia","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Douglas Xun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tse","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Fass","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-1818","authenticated-orcid":false,"given":"Gengqing","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_2","unstructured":"Latif, W., Lambrinos, K.J., Patel, P., and Rodriguez, R. (2025). Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs). StatPearls, StatPearls."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/dom.13172","article-title":"Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy","volume":"20","author":"Vilsboll","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Forzano, I., Varzideh, F., Avvisato, R., Jankauskas, S.S., Mone, P., and Santulli, G. (2022). Tirzepatide: A Systematic Update. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314631"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.JAA.0001007388.97793.41","article-title":"GLP-1 receptor agonists: A review of glycemic benefits and beyond","volume":"37","author":"Clark","year":"2024","journal-title":"JAAPA"},{"key":"ref_6","unstructured":"Collins, L., and Costello, R.A. (2025). Glucagon-Like Peptide-1 Receptor Agonists. StatPearls, StatPearls."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1001\/jama.2023.19574","article-title":"Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss","volume":"330","author":"Sodhi","year":"2023","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1139\/cjpp-2023-0464","article-title":"Discontinuing semaglutide after weight loss: Strategy for weight maintenance and a possible new side effect","volume":"102","author":"Carris","year":"2024","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_9","first-page":"438","article-title":"Prevalence of small intestinal bacterial overgrowth in patients with gastroparesis: A systematic review and meta-analysis","volume":"16","author":"Beas","year":"2023","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_10","first-page":"112","article-title":"Small intestinal bacterial overgrowth: A comprehensive review","volume":"3","author":"Dukowicz","year":"2007","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_11","first-page":"1071","article-title":"Small intestinal bacterial overgrowth (SIBO)\u2014Therapy, nutrition, microbiome","volume":"149","author":"Sellge","year":"2024","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_12","unstructured":"(2024, December 02). TriNetX. Available online: https:\/\/trinetx.com."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"370","author":"Altman","year":"2007","journal-title":"Lancet"},{"key":"ref_14","unstructured":"(2024, December 02). Exenatide: Drug Information Uptodate 2023. Available online: https:\/\/www.uptodate.com\/contents\/exenatide-drug-information?search=bydureon&source=panel_searchresult&selectedTitle=1~35&usage_type=panel&kp_tab=drug_general&display_rank=1#F595855."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1001\/jama.2015.13480","article-title":"The Propensity Score","volume":"314","author":"Haukoos","year":"2015","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/sim.5984","article-title":"The use of propensity score methods with survival or time-to-event outcomes: Reporting measures of effect similar to those used in randomized experiments","volume":"33","author":"Austin","year":"2014","journal-title":"Stat. Med."},{"key":"ref_17","first-page":"S5","article-title":"Burden of Illness in Type 2 Diabetes Mellitus","volume":"24","author":"Cannon","year":"2018","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"q1645","DOI":"10.1136\/bmj.q1645","article-title":"GLP-1 agonists: US sees 700% increase over four years in number of patients without diabetes starting treatment","volume":"386","author":"Mahase","year":"2024","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s40265-022-01746-8","article-title":"Tirzepatide: First Approval","volume":"82","author":"Syed","year":"2022","journal-title":"Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.eprac.2023.11.007","article-title":"Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis","volume":"30","author":"Ansari","year":"2024","journal-title":"Endocr. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13435","DOI":"10.1111\/obr.13435","article-title":"Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus-a systematic review and meta-analysis of randomized control trials","volume":"23","author":"Iqbal","year":"2022","journal-title":"Obes. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.sleep.2025.02.010","article-title":"Efficacy and safety of GLP-1 receptor agonists in the management of obstructive sleep apnea in individuals without diabetes: A systematic review and meta-analysis of randomized, placebo-controlled trials","volume":"129","author":"Kow","year":"2025","journal-title":"Sleep Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jalil, J.E., Gabrielli, L., Ocaranza, M.P., MacNab, P., Fernandez, R., Grassi, B., Jofre, P., Verdejo, H., Acevedo, M., and Cordova, S. (2024). New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084407"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, L., Chen, J., Wang, L., Chen, C., and Chen, L. (2022). Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1043789"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e73619","DOI":"10.2196\/73619","article-title":"Harnessing Facebook to Investigate Real-World Mentions of Adverse Events of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications: Observational Study of Facebook Posts From 2022 to 2024","volume":"5","author":"Alibilli","year":"2025","journal-title":"JMIR Infodemiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/ajg.2017.46","article-title":"Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus","volume":"112","author":"Rezaie","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1007\/s10620-020-06484-z","article-title":"Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates","volume":"66","author":"Cangemi","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_28","first-page":"e81891","article-title":"GLP-1 Receptor Agonists in Diabetes and Obesity: A Case Report and Review of Bowel Obstruction Risks and Management","volume":"17","author":"Jones","year":"2025","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2967\/jnmt.123.266800","article-title":"Glucagonlike Peptide-1 Receptor Agonists: The Good, the Bad, and the Ugly-Benefits for Glucose Control and Weight Loss with Side Effects of Delaying Gastric Emptying","volume":"52","author":"Parkman","year":"2024","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1002\/oby.23481","article-title":"Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial","volume":"30","author":"Maselli","year":"2022","journal-title":"Obesity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1136\/jim-2022-002480","article-title":"Frequency of GLP-1 receptor agonists use in diabetic patients diagnosed with delayed gastric emptying and their demographic profile","volume":"71","author":"Kalas","year":"2023","journal-title":"J. Investig. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kato, S., Sato, T., Fujita, H., Kawatani, M., and Yamada, Y. (2021). Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88612-x"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1086\/282697","article-title":"On r- and K-Selection","volume":"104","author":"Pianka","year":"1970","journal-title":"Am. Nat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1186\/s40064-016-2821-1","article-title":"Intestinal microbiota and chronic constipation","volume":"5","author":"Zhao","year":"2016","journal-title":"Springerplus"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:35Z","timestamp":1760035295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,7]]},"references-count":34,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15172264"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15172264","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,7]]}}}