Active surveillance research program for the assessment of the safety and the effectiveness of linagliptin

Study type

• Study type:
  Not applicable
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• If ‘Not applicable’, further details on the study type:
  Active surveillance, Sequential matched cohort study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  LINAGLIPTIN
• 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:
  120000

Study design details

• Main study objective:
  To conduct a multi-year research surveillance program that establishes and periodically updates initiator cohorts of linagliptin, within-class comparators (saxagliptin, sitagliptin, alogliptin), and out-of-class comparators (glitazones, 2nd generation of sulfonylureas (SUs)), and longitudinally follow them for the incidence of a variety of health outcomes.
• Outcomes:
  - Acute myocardial infarction- Coronary revascularization- Hemorrhagic stroke- Hospitalization for acute coronary syndrome- Ischemic stroke- Major adverse cardiovascular event (composite of coronary revascularization, hospitalization for acute coronary syndrome, ischemic and hemorrhagic stroke), - Heart failure hospitalization - Incident End-Stage Renal Disease (ESRD) - Acute renal failure (ARF)- ARF that requires dialysis
• Data analysis plan:
  We will receive new data as they become available on a periodic basis (every 6 months) and, at each data cut, we will update the original set of data, form sequential cohorts by propensity score (PS) matching within 6-month blocks of time, follow patients for each of the outcomes of interest in a prospective manner, and estimate measures of effect using person-time based analyses among patients who initiate linagliptin versus a comparator drug. Unadjusted and adjusted relative risks (hazard ratios) and rate differences will be estimated. In adjusted analyses, we will use propensity score (PS) matching to balance potential confounders.