{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:57:05Z","timestamp":1792069025631,"version":"4.4.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity. While their metabolic benefits are established, concerns persist about a possible link with gastrointestinal (GI) cancers. This study aimed to clarify the association between GLP-1 RA use and GI cancer risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A systematic search of PubMed, Embase, and Scopus till August 2024 identified randomized controlled trials (RCTs) reporting GI cancer outcomes. Ninety-three RCTs with 1.85 million participants were included. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model, with subgroup analyses by cancer type and exposure duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GLP-1 RA use was not associated with an increased overall risk of GI cancers (HR 0.81: 95% CI: 0.68\u20130.96). Subgroup analyses indicated reduced risks of colorectal cancer (HR 0.81: 95% CI: 0.68\u20130.96) and liver cancer (HR: 0.74; 95% CI: 0.62\u20130.88). Pancreatic cancer risk was not significantly elevated (HR: 0.78; 95% CI: 0.61\u20130.95). Findings were consistent across sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This meta-analysis of RCTs provides reassuring evidence that GLP-1 receptor agonists were not associated with an increased risk of gastrointestinal cancers, with signals suggesting a possible reduction in colorectal and liver cancer incidence that should be interpreted cautiously. These results support the continued safe use of GLP-1 RAs in T2DM and obesity, although longer trials with cancer-specific endpoints are warranted. This review was registered in Open Science Framework\n                      <jats:ext-link>https:\/\/osf.io\/3rv6d\/overview<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/osf.io\/3rv6d\/overview<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1736380","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:42:13Z","timestamp":1770709333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Reassessing cancer risk with GLP-1 receptor agonists: a comprehensive meta-analysis of gastrointestinal malignancies"],"prefix":"10.3389","volume":"17","author":[{"given":"Adil Farooq","family":"Wali","sequence":"first","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University","place":["Ras AlKhaimah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Rangraze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, RAK College of Medical Sciences, RAK Medical and Health Sciences","place":["Ras AlKhaimah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehla","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, RAK College of Medical Sciences, RAK Medical and Health Sciences University","place":["Ras AlKhaimah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwais Bashir","family":"Mufti","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals NHS Trust","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University","place":["Ras AlKhaimah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, RAK College of Medical Sciences, RAK Medical and Health Sciences","place":["Ras AlKhaimah, United Arab Emirates"]},{"name":"School of Medicine, PROMISE Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medicinal Specialties, University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/dom.12539","article-title":"Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial","volume":"17","author":"Ahmann","year":"2015","journal-title":"Diabetes Obes. 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