Comparative cardiovascular and renal effectiveness and safety of Empagliflozin and other SGLT2i in patients with type 2 diabetes (T2D), with and without baseline kidney disease in the United States

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Comparative effectiveness

Study drug and medical condition

• Name of medicine:
  JARDIANCE
• Medical condition to be studied:
  Diabetes mellitus

  Diabetic nephropathy

  End stage renal disease

  Cardiac death

  Myocardial infarction

  Acute kidney injury

  Hypovolaemia

  Urinary tract infection

  Diabetic ketoacidosis
• Additional medical condition(s):
  stroke, coronary revascularization, genital mycotic infections

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)
• Special population of interest:
  Renal impaired
• Estimated number of subjects:
  30400

Study design details

• Main study objective:
  The primary purpose of this research study is to determine the cardiovascular and renal effectiveness and safety associated with initiation of empagliflozin compared to initiation of DPP4i in patients with type 2 diabetes mellitus in the • Overall patient cohort, • Patients with established diabetic kidney disease, and • Patients without established diabetic kidney disease.
• Outcomes:
  A composite outcome including 40% decline in estimated glomerular filtration rate(eGFR), incident end-stage kidney disease, or all-cause mortality. 40% decline in eGFR End-stage kidney disease Dialysis Kidney transplant Composite hospitalization for heart failure (HHF) or all-cause mortality (ACM) HHF ACM Composite: myocardial infarction, stroke, ACM or coronary revascularization procedure Diabetic ketoacidosis Severe hypoglycemia Urinary tract cancer Severe urinary tract infections Acute kidney injury Genital mycotic infections
• Data analysis plan:
  Propensity score modeling with post-LASSO overlap weighting will be used to generate matched patient pairs across treatment groups. The effect of empagliflozin compared to DPP4i on outcomes will be assessed using Cox proportional hazards models in a 2-arm comparison. Incidence rates will be computed as the number of first events per 100 patient years of follow-up. Analyses of time to first event will be performed using Cox proportional hazards models. Outcomes where death is a competing risk will be analyzed using cause-specific proportional hazards models, achieved by censoring follow-up at the time of death. All analyses will be adjusted for covariates that continue to be unbalanced after reweighting, with any additional covariates of medical interest identified by the clinicians. Hazard ratios comparing empagliflozin to DPP4i with 95% confidence intervals and the adjusted p-value will be presented for all outcomes.