@article {Wonge001346, author = {Carlos K H Wong and Kenneth K C Man and Esther W Y Chan and Tingting Wu and Emily T Y Tse and Ian C K Wong and Cindy L K Lam}, title = {DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin{\textendash}sulfonylurea dual therapy with inadequate control}, volume = {8}, number = {1}, elocation-id = {e001346}, year = {2020}, doi = {10.1136/bmjdrc-2020-001346}, publisher = {BMJ Specialist Journals}, abstract = {Introduction This study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin{\textendash}sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methods We assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin{\textendash}sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.Results Over a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95\% CI 2.25 to 2.70, p\<0.001; 2.44, 95\% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95\% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95\% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95\% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95\% CI 1.09 to 1.71; 1.65, 95\% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.Conclusions For patients with T2DM on metformin{\textendash}sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.}, URL = {https://drc.bmj.com/content/8/1/e001346}, eprint = {https://drc.bmj.com/content/8/1/e001346.full.pdf}, journal = {BMJ Open Diabetes Research and Care} }