RRA-21430: Acute Pancreatitis in Patients with Type 2 Diabetes Who are New Users of Canagliflozin as Compared with New Users of Other Antihyperglycemic Agents: A Retrospective Cohort Study Using Large Claims Databases in the United States

Study type

• Study topic:
  Human medicinal product

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

  Disease epidemiology

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Post Authorization Safety Study (PASS)

Study drug and medical condition

• Name of medicine:
  INVOKANA
• Study drug International non-proprietary name (INN) or common name:
  CANAGLIFLOZIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A10BK02) canagliflozin

  canagliflozin
• Medical condition to be studied:
  Pancreatitis acute

Population studied

• Short description of the study population:
  Adult patients with T2DM who were newly exposed to a drug of interest (ie, canagliflozin or a comparator drug) between April 1, 2013 and September 30, 2017.
• 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)
• Special population of interest:
  Other
• Special population of interest, other:
  Type 2 diabetes mellitus patients
• Estimated number of subjects:
  354000

Study design details

• Main study objective:
  This observational, retrospective, new-user cohort study aims to 1. Estimate the incidence rate of acute pancreatitis in type 2 diabetes (T2D) patients newly exposed to canagliflozin and comparator antihyperglycemic agents (AHAs), and 2. Compare the hazard of acute pancreatitis in T2D patients newly exposed to canagliflozin vs. comparator AHAs, based on propensity-score matched cohorts.
• Outcomes:
  Acute pancreatitis
• Data analysis plan:
  Descriptive statistics of incidence rate will be presented. Comparative analysis will be conducted using both ITT and PP approaches for new users of canagliflozin vs. new users of alternative AHA therapy. Conditional Cox proportional hazards model based on time-to-first event approach, using propensity-score matched sets (with variable matching), will be used to estimate the comparative treatment effect size. The propensity score will be estimated through large-scale regularized regression, with demographics, all prior conditions/drugs/procedures, risk scores, utilization density as baseline covariates. Hochberg step-up procedure will be applied and adjusted p-values will be reported in addition to empirical p-values to control for multiple comparisons. A set of negative control outcomes will also be used to calibrate empirically observed p-values. Patients with a history of any form of pancreatitis will be evaluated and included in the study, if balance at baseline is achieved.