Post-authorisation safety study to assess the risk of urinary tract malignancies in relation to empagliflozin exposure in patients with type 2 diabetes: a multi-database European study (PASS DiabCancer)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10BD20) metformin and empagliflozin

  metformin and empagliflozin
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  56100

Study design details

• Main study objective:
  The main objective of the study is to estimate, among patients with type 2 diabetes mellitus, the risk of all urinary tract cancers and those of bladder and renal cancers also separately in patients initiating empagliflozin compared to patients initiating a DPP-4 inhibitors and to patients initiatin
• Outcomes:
  The primary outcomes of interest for this study are urinary tract cancers, bladder cancer, and renal cancer. The secondary outcome of interest for this study is non-renal, non-bladder urinary tract cancers (referred to as other urinary tract cancers). Non-renal, non-urinary bladder urinary tract cancers include ureter and urethra cancers.
• Data analysis plan:
  The main data analyses will be conducted in two stages: (i) construction of the propensity score (PS)-matched cohorts (for each comparison) (ii) estimating the effect of exposure to empagliflozin on the outcomes using adjusted hazard ratio compared to those exposed to DPP-4 inhibitor or SGLT-2 inhibitor and their respective incidence rates. ; Patients starting combination of empagliflozin and metformin (fixed-dose or free combination) will be compared with patients starting combination of another DPP-4 inhibitor or SGLT-2 inhibitor and metformin. ; Incidence rates (crude and adjusted) will be presented for each exposure group and stratified by relevant variables using the Poisson regression approach. Relative risks will be presented as hazard ratios adjusted for relevant variables using the Cox’s proportional hazards model with the time-varying covariate approach. ; The adjusted hazard ratios and incidence rates will be presented along with 95% confidence intervals for the risk estimate