Post-authorisation safety study in patients with type 2 diabetes mellitus to assess the risk of acute liver injury, acute kidney injury and chronic kidney disease, severe complications of urinary tract infection, genital infections, and diabetic ketoacidosis among patients treated with empagliflozin compared to patients treated with DPP-4 inhibitors (PASS renal, liver injury, infection, ketoacidosis)

Study type

• Study topic:
  Disease /health condition

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

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

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Observational study

Study drug and medical condition

• Name of medicine:
  Jardiance

  Synjardy
• Study drug International non-proprietary name (INN) or common name:
  EMPAGLIFLOZIN

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

  (A10BH01) sitagliptin

  (A10BH02) vildagliptin

  (A10BH03) saxagliptin

  (A10BH04) alogliptin

  (A10BH05) linagliptin

  (A10BK03) empagliflozin
• Medical condition to be studied:
  Type 2 diabetes mellitus
• Additional medical condition(s):
  Acute liver injury

Population studied

• Short description of the study population:
  Patients aged 18 years or older diagnosed with type 2 diabetes received treatment with empagliflozin or DPP-4 inhibitor identified from the Clinical Practice Research Datalink (CPRD) database for the study period of August 2014 to August 2019.; Inclusion criteria:; · Be aged 18 or more years at the index date.; · Have at least 12 months of continuous registration before or at the index date. In the CPRD this means registration in a primary care practice with up-to-standard data. In Denmark, this means residency in the country. In the HIRD, this means enrolment in the health care plan.; · Have T2D ever before or at the index date: the algorithm to identify patients with T2D will be adapted to the type of data available in each data source. This algorithm may include medication codes and will be described in the statistical epidemiological analysis plan.; ; Exclusion criteria:; · Patients with a confirmed diagnosis of T1D before or at the index date will be excluded from the study.; · Patients prescribed/dispensed combinations of SGLT2 inhibitors with DPP-4 inhibitors at the index date (as fixed-dose combinations such as Glyxambi® [empagliflozin and linagliptin], or as non–fixed-dose combinations of the two individual medications prescribed on the same date) will be excluded.
• 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:
  151184

Study design details

• Main study objective:
  To estimate, among patients with type 2 diabetes mellitus, the risk of acute liver injury, acute kidney injury and chronic kidney disease, severe complications of urinary tract infections, genital infections and diabetic ketoacidosis among patients treated with empagliflozin compared with patients treated with dipeptidyl peptidase-4 inhibitors.
• Outcomes:
  Acute liver injury, acute kidney injury, severe complications of urinary tract infection, genital infections, diabetic Ketoacidosis, acute liver injury in a subset of patients with or without predisposing factors, chronic kidney disease, severe genital infections
• Data analysis plan:
  The following estimates and comparisons will be generated: Crude and adjusted incidence rates of each of the outcomes among empagliflozin new users and DPP-4 inhibitor new users. Incidence rates will be reported as point estimates (in cases per 1,000 person-years) and 95% confidence intervals (CIs). Summary IRRs, after adjusting for propensity score deciles, among empagliflozin new users vs. DPP-4 inhibitor new users. The adjusted IRRs for each of the primary outcomes will be the main effect estimates of interest. Adjusted incidence rates and IRRs will be calculated using analytic techniques involving stratification by categories of propensity scores. An additional analysis will further stratify the IRRs by categories of insulin use at the index date. Sensitivity analyses will be performed to evaluate the potential for other sources of bias and confounding. Meta-analytic methods will be used to combine the IRRs obtained from the main analysis performed by all the data sources.

Documents

Study results

1245-0096_Synopsis_Redacted

Study, other information

1245-0096--protocol_revision-04_Redacted

Study publications

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of …

Time between laboratory tests and acute liver and kidney injury diagnosis codes…