{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:12:03Z","timestamp":1790953923496,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T00:00:00Z","timestamp":1670716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Some early reports in the medical literature have raised concern about a possible increased risk of pancreatic cancer associated with the use of two broad classes of incretin\u2010based therapies, dipeptidyl peptidase\u20104 inhibitors, and glucagon\u2010like peptide\u20101 receptor agonists. This possibility has been somewhat mitigated by the null findings meta\u2010analyses of randomized controlled trials, but the usefulness of their findings was hampered by serious shortcomings of lack of power and representativeness. These shortcomings can typically be addressed by observational studies, but observational studies on the topic have yielded conflicting findings. A systematic review and meta\u2010analysis of observational studies was performed to qualitatively and quantitatively appraise the totality of evidence on the association between the use of incretin\u2010based therapies and the risk of pancreatic cancer in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PubMed, Web of Science, Embase, and Google Scholar databases were searched. The study quality was appraised using the ROBINS\u2010I tool and based on the presence of pharmacoepidemiology biases. A random\u2010effects model was used to estimate the summary relative risks with corresponding CIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 14 studies were included. The qualitative assessment revealed that all studies had inadequate follow\u2010up (\u22645\u2009years), 12 studies were suspected to suffer from time\u2010lag bias (due to inappropriate choice of comparator group) to varying extent, five studies included prevalent users, five studies did not implement exposure lag period, five studies had a serious risk of bias due to confounding, and one study had a time\u2010window bias. The quantitative assessment showed no indication of an increased risk when all studies were pooled together (RR 1.04, 95% CI 0.87, 1.24) and when the analysis was restricted to the studies with the least bias (RR 0.77, 95% CI 0.51, 1.17). However, the pooled RRs were more frequently higher in the studies with less rigorous design and analysis. Specifically, a tendency toward an increased risk was observed in the studies with (RR 1.34, 95% CI 1.04, 1.72) or possibly with (RR 1.10, 95% CI 0.89, 1.36) time\u2010lag bias, in the studies that did not apply (RR 1.23, 95% CI 0.93, 1.63) or with potentially inadequate exposure lag period of 6\u00a0months (RR 1.13, 95% CI 0.66, 1.94), in the studies that inappropriate comparator group of a combination of unspecified (RR 1.49, 95% CI 1.25, 1.78) or non\u2010insulin (RR 1.15, 95% CI 0.93, 1.42) antidiabetic drugs, and in the studies with serious risk of bias due to confounding (RR 1.18, 95% CI 0.56, 2.49).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, the totality of evidence from observational studies does not support the claim that the use of incretin\u2010based therapies is associated with an increased risk of pancreatic cancer in routine clinical practice. The increased risk of pancreatic cancer observed in observational studies reflects bias resulting from suboptimal methodological approaches, which need to be avoided by future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.5550","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:19:08Z","timestamp":1665620348000},"page":"107-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A systematic review and meta\u2010analysis of observational studies of the association between the use of incretin\u2010based therapies and the risk of pancreatic cancer"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-6969","authenticated-orcid":false,"given":"Khemayanto","family":"Hidayat","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of Soochow University  Suzhou 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