Phyo T Htoo1, John B Buse2, Mugdha Gokhale1, M Alison Marquis3, Virginia Pate1, Til Stürmer4. 1. Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Campus Box 7435, 2101 McGavran-Greenberg Hall, Chapel Hill, NC, USA. 2. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. 3. Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 4. Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Campus Box 7435, 2101 McGavran-Greenberg Hall, Chapel Hill, NC, USA. sturmer@unc.edu.
Abstract
AIMS: Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence. METHODS: We conducted a cohort study on US Medicare beneficiaries over age 66 from 2007 to 2013 without prevalent cancer. We identified three active-comparator and new-user cohorts: DPP-4i versus thiazolidinediones (TZD), DPP-4i versus sulphonylureas (SU), and GLP-1ra versus long acting insulin (LAI). Follow-up started from 6 months post-second prescription and ended 6 months after stopping (primary as-treated analysis). We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for incident colorectal cancer adjusting for measured confounders using propensity score weighting. RESULTS: The median duration of treatment ranged 0.7-0.9 years among DPP-4i cohorts. Based on 104 events among 39,334 DPP-4i and 63 events among 25,786 TZD initiators, there was no association between DPP-4i initiation and colorectal cancer (adjusted HR = 1.17 (CI 0.88, 1.71)). There were 73 events among 27,047 DPP-4i and 266 events among 76,012 SU initiators with the adjusted HR 0.98 (CI 0.74, 1.30). We identified 5600 GLP-1ra and 54,767 LAI initiators and the median duration of treatment was 0.8 and 1.2 years, respectively. The adjusted HR was 0.82 (CI 0.42, 1.58) based on <11 events among GLP-1ra versus 276 events among LAI initiators. CONCLUSION: Although limited by the short duration of treatment, our analyses based on real-world drug utilization patterns provide evidence of no short-term effect of incretin-based agents on colorectal cancer.
AIMS: Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence. METHODS: We conducted a cohort study on US Medicare beneficiaries over age 66 from 2007 to 2013 without prevalent cancer. We identified three active-comparator and new-user cohorts: DPP-4i versus thiazolidinediones (TZD), DPP-4i versus sulphonylureas (SU), and GLP-1ra versus long acting insulin (LAI). Follow-up started from 6 months post-second prescription and ended 6 months after stopping (primary as-treated analysis). We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for incident colorectal cancer adjusting for measured confounders using propensity score weighting. RESULTS: The median duration of treatment ranged 0.7-0.9 years among DPP-4i cohorts. Based on 104 events among 39,334 DPP-4i and 63 events among 25,786 TZD initiators, there was no association between DPP-4i initiation and colorectal cancer (adjusted HR = 1.17 (CI 0.88, 1.71)). There were 73 events among 27,047 DPP-4i and 266 events among 76,012 SU initiators with the adjusted HR 0.98 (CI 0.74, 1.30). We identified 5600 GLP-1ra and 54,767 LAI initiators and the median duration of treatment was 0.8 and 1.2 years, respectively. The adjusted HR was 0.82 (CI 0.42, 1.58) based on <11 events among GLP-1ra versus 276 events among LAI initiators. CONCLUSION: Although limited by the short duration of treatment, our analyses based on real-world drug utilization patterns provide evidence of no short-term effect of incretin-based agents on colorectal cancer.
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Authors: Jian Gong; Carolyn Hutter; John A Baron; Sonja Berndt; Bette Caan; Peter T Campbell; Graham Casey; Andrew T Chan; Michelle Cotterchio; Charles S Fuchs; Steven Gallinger; Edward Giovannucci; Tabitha Harrison; Richard Hayes; Li Hsu; Shuo Jiao; Yi Lin; Noralane M Lindor; Polly Newcomb; Bethann Pflugeisen; Amanda I Phipps; Thomas Rohan; Robert Schoen; Daniela Seminara; Martha L Slattery; Deanna Stelling; Fridtjof Thomas; Greg Warnick; Emily White; John Potter; Ulrike Peters Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-09-20 Impact factor: 4.254