| アブストラクト | OBJECTIVE: To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. DESIGN: Population based cohort study. SETTING: General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS: 154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. MAIN OUTCOME MEASURES: Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. RESULTS: During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). CONCLUSION: Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. |
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| 投稿者 | Abrahami, Devin; Douros, Antonios; Yin, Hui; Yu, Oriana Hy; Faillie, Jean-Luc; Montastruc, Francois; Platt, Robert W; Bouganim, Nathaniel; Azoulay, Laurent |
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| 組織名 | Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital,;3755 Cote Sainte-Catherine Road, H425.1, Montreal, QC, H3T 1E2, Canada.;Department of Epidemiology, Biostatistics, and Occupational Health, McGill;University, Montreal, QC, Canada.;Institute of Clinical Pharmacology and Toxicology, Charite University Medicine;Berlin, Berlin, Germany.;Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.;Department of Medical Pharmacology and Toxicology, CHU Montpellier; Laboratory of;Biostatistics, Epidemiology and Public Health, University of Montpellier,;Montpellier, France.;Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and;Pharmacoepidemiology, INSERM UMR 1027, CIC 1426, Toulouse University Hospital,;Faculty of Medicine, University of Toulouse, France.;Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.;Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.;3755 Cote Sainte-Catherine Road, H425.1, Montreal, QC, H3T 1E2, Canada;laurent.azoulay@mcgill.ca. |
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