| Abstract: | BACKGROUND: The risk of pancreatic cancer associated with incretin-based therapies is controversial. METHODS: This study retrospectively analyzed 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 December 31, 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 3,658 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. |
