{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:15:47Z","timestamp":1792088147566,"version":"4.4.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Tri-Service General Hospital Beitou Branch","award":["TSGH-BT-X-115006"],"award-info":[{"award-number":["TSGH-BT-X-115006"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors are widely prescribed for their cardiometabolic benefits, yet their hematologic oncologic safety remains uncertain. Because hematologic malignancies are highly lethal and biologically heterogeneous, delineating drug-specific risks across histopathologic subtypes is clinically crucial. This histopathology-stratified network meta-analysis (NMA) evaluated and compared the hematologic malignancy risks associated with individual agents from these drug classes. Following Cochrane guidance for adverse-event synthesis, we conducted this frequentist-based NMA of randomized controlled trials (RCTs). The primary endpoint was incident hematologic malignancy, categorized a priori into leukemia (acute and chronic forms), lymphoma (Hodgkin and non-Hodgkin), and myeloma\/plasma cell neoplasms. Bayesian models were used as sensitivity analyses. Seventy-five RCTs including 270,471 participants were eligible. Dulaglutide was associated with a significantly increased risk of overall hematologic malignancy (RR = 2.17, 95% CIs = 1.14\u20134.17). In contrast, tirzepatide (RR = 0.22, 95% CIs = 0.06\u20130.78) and linagliptin (RR = 0.51, 95% CIs = 0.27\u20130.95) were linked to a reduced overall risk. In histopathology-specific analyses, tirzepatide showed a significant protective association against non-Hodgkin\u2019s lymphoma, whereas no agent demonstrated clear signals for leukemia or myeloma. In this histopathology-focused NMA, dulaglutide emerged as the only agent with a significantly elevated overall hematologic malignancy risk, whereas tirzepatide and linagliptin exhibited protective profiles. The lymphoma-specific benefit observed for tirzepatide underscores the value of histologic subclassification when evaluating oncologic safety of antidiabetic therapies and calls for targeted mechanistic and long-term outcome studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>PROSPERO CRD420251151419. The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical University (TSGHIRB E202516007).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13045-026-01788-5","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:29:32Z","timestamp":1775723372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Agent-specific, histopathology-stratified hematologic malignancy risk among dpp-4 inhibitors, glp-1 receptor agonists, and SGLT2 inhibitors: a network meta-analysis of 270,471 participants"],"prefix":"10.1186","volume":"19","author":[{"given":"Pao-Yen","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Syuan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiann-Jy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Yan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mein-Woei","family":"Suen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Ming","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon","family":"Stubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Te","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Pin","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-5028","authenticated-orcid":false,"given":"Yow-Ling","family":"Shiue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Pin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ta","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-7800","authenticated-orcid":false,"given":"Ping-Tao","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1138-5586","authenticated-orcid":false,"given":"Chih-Sung","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"1788_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216793","volume":"595","author":"J Yang","year":"2024","unstructured":"Yang J, Liu X, Zhong QZ, Yang Y, Wu T, Chen SY, et al. Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: a global data analysis. Cancer Lett. 2024;595:216793.","journal-title":"Cancer Lett"},{"issue":"11","key":"1788_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/biom15111622","volume":"15","author":"PY Lin","year":"2025","unstructured":"Lin PY, Zeng BY, Hsu CW, Suen MW, Hung CM, Stubbs B, et al. Divergent risks of hematologic malignancies associated with GLP-1 receptor agonists and sglt2 inhibitors: preliminary findings from a pilot network meta-analysis. Biomolecules. 2025;15(11):1622.","journal-title":"Biomolecules"},{"key":"1788_CR3","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1177\/1536867X1501500403","volume":"15","author":"IR White","year":"2015","unstructured":"White IR. Network meta-analysis. 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Lancet Psychiatry. 2020;7(1):64\u201377.","journal-title":"Lancet Psychiatry"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-026-01788-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-026-01788-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-026-01788-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:40:02Z","timestamp":1781646002000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13045-026-01788-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1788"],"URL":"https:\/\/doi.org\/10.1186\/s13045-026-01788-5","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"assertion":[{"value":"29 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current study did not directly involve individual participant so that we did not have the chance to approach individual participant or explore individual participant\u2019s information. Therefore, it is impossible to obtain consent to participate in the current study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent to participate and publish"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23"}}