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Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort included patients with type 2 diabetes mellitus who were prescribed GLP-1RAs or other nonglucagon-like peptide-1 receptor agonist antidiabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other nonglucagon-like peptide-1 receptor agonist antidiabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan\u2013Meier survival analysis, with the hazard ratio and 95% confidence interval calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study population comprised 1\u200a636\u200a056 eligible patients including 167\u200a091 prescribed GLP-1RAs and 1\u200a468\u200a965 prescribed other antidiabetes medications. GLP-1RAs were associated with a statistically significant decreased risk for pancreatic cancer incidence compared with each of 6 nonglucagon-like peptide-1 receptor agonist antidiabetes medications with hazard ratios ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with type 2 diabetes mellitus. Further studies and trials are needed to explore mechanisms and confirm causal effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djae260","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T23:20:12Z","timestamp":1729034412000},"page":"476-485","source":"Crossref","is-referenced-by-count":57,"title":["Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data"],"prefix":"10.1093","volume":"117","author":[{"given":"Lindsey","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Science, Health, and Society, Case Western Reserve University School of Medicine , Cleveland, OH 44106,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QuanQiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine , Cleveland, 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