Investigating risk of cancer with Sodium-glucose cotransporter 2 inhibitors: a Case/Non-Case Study in the WHO Global Pharmacovigilance Database Vigibase

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Case non-case design (disproportionnality analysis)

Study drug and medical condition

• Name of medicine:
  DAPAGLIFLOZIN
• Name of medicine, other:
  Canagliflozin, Empagliflozin
• Study drug International non-proprietary name (INN) or common name:
  CANAGLIFLOZIN

  DAPAGLIFLOZIN

  EMPAGLIFLOZIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A10BK) Sodium-glucose co-transporter 2 (SGLT2) inhibitors

  Sodium-glucose co-transporter 2 (SGLT2) inhibitors

  (A10BK01) dapagliflozin

  dapagliflozin

  (A10BK02) canagliflozin

  canagliflozin

  (A10BK03) empagliflozin

  empagliflozin
• Additional medical condition(s):
  Cancer

Population studied

• Short description of the study population:
  Adults > 18 years old exposed to SGLT-2i or other oral antidiabetic drugs (GLP1 analogues and DPP4 inhibitors) in Vigibase between 2014 and 2023
• Age groups:
  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)

Study design details

• Study design:
  Disproportionnality analysis on the WHO global database Vigibase.
• Main study objective:
  Exploratory analysis in the WHO's global pharmacovigilance database, Vigibase, to search for main cancers risk signals associated with the use of SGLT-2i.
• Setting:
  All ICSR between 01/01/2014 and 31/12/2023 were included. Patients 18 years old or older will be included. Cases are each subtype of cancer and non cases are all other ICSRs of the database. Exposed patients are ICSR with SGLT-2i (empagliflozin, dapagliflozin, canagliflozin) as suspected drug, controls are ICSR with GLP-1 analogues or DPP4 inhibitors as suspected drug.
• Comparators:
  Patients exposed to GLP-1 analogues or DPP4 inhibitors
• Outcomes:
  Reprorting Odds Ratios for cancers (overall) and each cancer taken individually.
• Data analysis plan:
  The characteristics of the subjects in both groups will be described using frequencies and percentages. The disproportionality in cancer reporting between the exposed and non-exposed groups will be analyzed by calculating the Reporting Odds Ratio (ROR) through logistic regression with adjustments for age, sex, reporting country, and co-prescriptions with carcinogenic risk. The signal will be considered significant if the lower bound of the 95% confidence interval (CI95%) is greater than 1.