title: Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Phyo T
authors.initials: PT
authors.lastname: Htoo
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: 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.
authors.forename: Mugdha
authors.initials: M
authors.lastname: Gokhale
authors.affiliation: Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: M Alison
authors.initials: MA
authors.lastname: Marquis
authors.affiliation: 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.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pate
authors.affiliation: 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.
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Cohort study; Colorectal cancer; Comparative effectiveness research; Dipeptidyl peptidase-4 inhibitors; Glucagon-like peptide-1 receptor agonists; Pharmacoepidemiology