title: Sitagliptin and pancreatic cancer risk in patients with type 2 diabetes.
abstract: BACKGROUND
  The risk of pancreatic cancer associated with incretin-based therapies is controversial.
  
  
  METHODS
  This study retrospectively analysed the National Health Insurance database including patients with newly diagnosed type 2 diabetes mellitus at an age ≥ 25 years between 1999 and 2010. A total of 71 137 ever users of sitagliptin and 933 046 never users were followed for pancreatic cancer until 31 December 2011. A time-dependent approach was used to calculate incidence and estimate hazard ratios adjusted for propensity score using Cox regression.
  
  
  RESULTS
  During follow-up, 83 ever users and 3658 never users developed pancreatic cancer, representing an incidence of 73·6 and 55·0 per 100 000 person-years, respectively. The adjusted hazard ratio (95% confidence intervals) for ever versus never users was 1·40 (1·13-1·75). The respective adjusted hazard ratio for the first, second and third tertile of cumulative dose < 14 700, 14 700-33 700 and > 33 700 mg was 1·83 (1·28-2·62), 1·97 (1·41-2·76) and 0·72 (0·45-1·15). For average daily dose of < 50, 50-99·9 and ≥ 100 mg, the respective hazard ratio was 3·10 (1·17-8·26), 1·01 (0·63-1·61) and 1·53 (1·18-1·97).
  
  
  CONCLUSIONS
  Sitagliptin is significantly associated with a higher risk of pancreatic cancer, especially when the cumulative dose is < 33 700 mg. The risk diminished in users with a higher cumulative dose. The daily dose of sitagliptin should better be kept < 100 mg, and its use should be reconsidered in patients who suffer from severe renal impairment and thus a daily dose of < 50 mg is always recommended. Future studies are required to confirm the findings with more appropriate adjustment for smoking.
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000453:epidemiology; D021441:Carcinoma, Pancreatic Ductal / Q000453:epidemiology*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D000068900:Sitagliptin Phosphate
keywords: Incretin; National Health Insurance; Taiwan; pancreatic cancer; sitagliptin