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.

Keywords: Incretin; National Health Insurance; Taiwan; pancreatic cancer; sitagliptin.