{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:16:19Z","timestamp":1792088179915,"version":"4.4.0"},"reference-count":65,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T00:00:00Z","timestamp":1726963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. Methods: We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of &gt;25 kg\/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients\u2019 baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. Results: A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p &lt; 0.0001) and esophageal cancer (0.04% vs. 0.13%, p &lt; 0.0001) at the seven-year mark. Conclusion: The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.<\/jats:p>","DOI":"10.3390\/cancers16183224","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"3224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6518-3971","authenticated-orcid":false,"given":"Mark","family":"Ayoub","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3222-9454","authenticated-orcid":false,"given":"Rafi","family":"Aibani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiana","family":"Dodd","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed","family":"Ceesay","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Bhinder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Faris","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bayonne Medical Center, Bayonne, NJ 07002, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisar","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-1704","authenticated-orcid":false,"given":"Ebubekir","family":"Daglilar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1001\/jamaoncol.2023.5573","article-title":"GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients with Type 2 Diabetes, with and without Overweight\/Obesity","volume":"10","author":"Wang","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_2","first-page":"1","article-title":"Risk of Malignant Neoplasia with Glucagon-like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis","volume":"2019","author":"Liu","year":"2019","journal-title":"J. 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