Abstract
OBJECTIVES: To study the association between exposures to glucose-lowering therapy and risk of cancer using the nationwide administrative registers in Denmark. DESIGN: Nationwide cohort study. SETTING: All hospitals in Denmark. PARTICIPANTS: All individuals aged ≥35 years in 1998-2009 who were naive to glucose-lowering treatment and had no history of cancer. Primary measures outcomes: first cancer diagnosis between 1998 and 2009. The RR of cancer as dependent on exposure to individual glucose-lowering agents was assessed by multivariable Poisson regression models. RESULTS: Of 159 894 patients that initiated treatment with glucose-lowering agents, 12 789 developed cancer, incidence rate 17.4/1000 person-years. Of the remaining 3 447 904 individuals not using glucose-lowering agents, 293 878 developed cancer, incidence rate 7.9/1000 person-years. Use of different types of glucose-lowering agents including human insulin, insulin analogues, as well as sulfonylureas were associated with a quantitatively similar and significantly increased RR of cancer of 1.2-1.3 compared with unexposed individuals after multivariable adjustment. For the majority of agents, the authors identified the highest RR of cancer during the first 30 treatment days with a subsequent decline of risk approaching the cancer risk of the background population only 6-12 months after initiation of treatments. CONCLUSIONS: Use of most glucose-lowering agents including sulfonylureas was associated with a comparable increased risk of cancer shortly after initiation of treatment and subsequently a decline to the risk of the background population. This suggests that the relation is not causal.