title: Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study.
abstract: OBJECTIVE
  To compare pancreatic cancer incidence and diagnostic evaluation among patients initiating dipeptidyl-peptidase-4 (DPP-4) inhibitor treatment with those initiating sulfonylureas (SU) and thiazolidinediones (TZD).
  
  
  METHODS
  Medicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4 inhibitors, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreatic cancer. Diagnostic evaluations were compared using risk ratios.
  
  
  RESULTS
  In the DPP-4 inhibitor versus SU comparison, there were 18 179 patients who initiated treatment with DPP-4 inhibitors, of whom 26 developed pancreatic cancer (interquartile range follow-up 5-18 months). In the DPP-4 inhibitor versus TZD comparison there were 29 366 people initiating DPP-4 inhibitor treatment and 52 of these developed pancreatic cancer. The risk of pancreatic cancer with DPP-4 inhibitor treatment was lower relative to SU treatment (HR: 0.6, CI: 0.4-0.9) and similar to TZD treatment (HR: 1.0, 95% CI: 0.7-1.4). After the first 6 months of follow-up were excluded to reduce the potential for reverse causality, the results were not altered. The probability of diagnostic evaluation after commencing DPP-4 inhibitor treatment (79.3%) was similar to that for TZD (74.1%, risk ratio 1.06, 95% CI: 1.05-1.07) and SU (74.6%) (risk ratio 1.06, 95% CI: 1.05-1.07). The probability of diagnostic evaluation before the index date (date of initiating treatment) was ∼80% for all cohorts.
  
  
  CONCLUSIONS
  Although the present study was limited by sample size and the observed duration of treatment in the USA, our well-controlled population-based study suggests there is no higher short-term pancreatic cancer risk with DPP-4 inhibitor treatment relative to SU or TZD treatment.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gokhale
authors.forename: J B
authors.initials: JB
authors.lastname: Buse
authors.forename: C L
authors.initials: CL
authors.lastname: Gray
authors.forename: V
authors.initials: V
authors.lastname: Pate
authors.forename: M A
authors.initials: MA
authors.lastname: Marquis
authors.forename: T
authors.initials: T
authors.lastname: Stürmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D006278:Medicare; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D057216:Propensity Score; D016016:Proportional Hazards Models; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones
keywords: DPP-IV inhibitor; antidiabetic drug; incretin therapy
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