Chin-Hsiao Tseng1,2,3. 1. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 3. Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan.
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.
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: Laurent Azoulay; Kristian B Filion; Robert W Platt; Matthew Dahl; Colin R Dormuth; Kristin K Clemens; Madeleine Durand; David N Juurlink; Laura E Targownik; Tanvir C Turin; J Michael Paterson; Pierre Ernst Journal: BMJ Date: 2016-02-17