To study the association between exposures to glucose-lowering therapy and risk of cancer using the nationwide administrative registers in Denmark.
Nationwide cohort study.
All hospitals in Denmark.
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.
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.
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.
Several observational studies have suggested that insulin therapy may increase the risk of cancer. If insulin therapy causes/enhances cancer development, the RR would be expected to increase with longer treatment duration.
The present study investigated the association between treatment duration with individual glucose-lowering agents and the RR of developing cancer in 3.6 million individuals.
Use of human insulin, insulin analogues and sulfonylureas were associated with a significantly increased RR of cancer of 1.2–1.3 compared with unexposed individuals.
For all agents, the highest RR of cancer was found during the first 30 days of treatment. Hereafter, the RR declined rapidly, reaching a RR of cancer comparable to unexposed individuals after only 6–12 months of therapy for most agents.
This strongly suggests that a previously reported association between use of glucose-lowering agents and increased risk of cancer is not causal.
Strengths and limitations of this study
This study was based on complete and nationwide administrative registers, thereby reducing selection bias.
Data on measurements on body mass index, glucose regulation and family cancer history were lacking.