{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:10:22Z","timestamp":1778101822237,"version":"3.51.4"},"reference-count":200,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium\u2013glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01\u20136.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg\/day) showed the clearest signal (OR 3.42, 95% CI 1.08\u201310.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24\u20130.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction.<\/jats:p>","DOI":"10.3390\/ijms27020608","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:43Z","timestamp":1767786403000},"page":"608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Agent- and Dose-Specific Intestinal Obstruction Safety of GLP-1 Receptor Agonists and SGLT2 Inhibitors: A Network Meta-Analysis of Randomized Trials"],"prefix":"10.3390","volume":"27","author":[{"given":"Jiann-Jy","family":"Chen","sequence":"first","affiliation":[{"name":"Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan"},{"name":"Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-4060","authenticated-orcid":false,"given":"Chih-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Ming","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan"},{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-0322","authenticated-orcid":false,"given":"Mein-Woei","family":"Suen","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan"},{"name":"Gender Equality Education and Research Center, Asia University, Taichung 41354, Taiwan"},{"name":"Department of Medical Research, Asia University Hospital, Asia University, Taichung 41354, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung 80276, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chieh","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ping An Medical Clinic, Tainan 708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendon","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"},{"name":"Department of Sport, University of Vienna, 1010 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-1311","authenticated-orcid":false,"given":"Tien-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Tri-Service General Hospital, Taipei 114202, Taiwan"},{"name":"Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei 114202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Te","family":"Lei","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy, Immunology, and Rheumatology, Department of Pediatrics, Hsinchu Municipal MacKay Children\u2019s Hospital, Hsinchu 30068, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3220, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Pin","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan"},{"name":"Department of Neurology, E-Da hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-5028","authenticated-orcid":false,"given":"Yow-Ling","family":"Shiue","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing-Yan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Ta","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112201, Taiwan"},{"name":"Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Institute of Brain Science and Brain Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-2502","authenticated-orcid":false,"given":"Kuan-Pin","family":"Su","sequence":"additional","affiliation":[{"name":"Mind-Body Interface Research Center (MBI Lab & Care), China Medical University Hospital, Taichung 40447, Taiwan"},{"name":"Office of Research and Development, Asia University, Taichung 413305, Taiwan"},{"name":"College of Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"An-Nan Hospital, China Medical University, Tainan 709, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Sung","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical University, Taipei 114202, Taiwan"},{"name":"Department of Psychiatry, National Defense Medical University, Taipei 114202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing-Syuan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-7800","authenticated-orcid":false,"given":"Ping-Tao","family":"Tseng","sequence":"additional","affiliation":[{"name":"Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 81166, Taiwan"},{"name":"Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S2213-8587(22)00247-9","article-title":"Glucose-lowering drugs with cardiovascular benefits as modifiers of critical elements of the human life history","volume":"10","author":"Avogaro","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/s41591-024-03412-w","article-title":"Mapping the effectiveness and risks of GLP-1 receptor agonists","volume":"31","author":"Xie","year":"2025","journal-title":"Nat. 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