Dipeptidyl-peptidase-4 Inhibitors and Pancreatic Cancer: A Cohort Study

Diabetes Obes Metab. 2014 Dec;16(12):1247-56. doi: 10.1111/dom.12379. Epub 2014 Sep 10.


Aim: 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.

Conclusion: 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.

Keywords: DPP-IV inhibitor; antidiabetic drug; incretin therapy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Male
  • Medicare
  • Middle Aged
  • Odds Ratio
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / epidemiology*
  • Propensity Score
  • Proportional Hazards Models
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects*
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects*
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones