Cardiovascular and renal outcomes, and mortality in Danish patients with type 2 diabetes who initiate empagliflozin versus GLP1-RA: A Danish nationwide comparative effectiveness study (EMPLACE)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Effectiveness study (incl. comparative)

  Healthcare resource utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort
• Non-interventional study design, other:
  Nationwide population-based comparative effectiveness cohort study based on prospective medical databases in Denmark

Study drug and medical condition

• Medicinal product name:
  JARDIANCE

  GLYXAMBI

  SYNJARDY

  BYDUREON

  VICTOZA

  LYXUMIA

  TRULICITY

  OZEMPIC

  RYBELSUS

  XULTOPHY

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

  LIRAGLUTIDE
• 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)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Pregnant women

  Renal impaired
• Estimated number of subjects:
  50000

Study design details

• Main study objective:
  Our primary objective is to compare clinical outcomes (cardiovascular events, mortality) among empagliflozin initiators and liraglutide initiators in Denmark.
• Outcomes:
  Primary outcome is a composite of hospitalization due to stroke, myocardial infarction, unstable angina, coronary revascularization, heart failure (HF), or all-cause death (expanded MACE). Secondary outcomes are first hospital admission with a diagnosis of HF and/or initiation of loop diuretics, hospital admission with HF and/or all-cause death, composite of all-cause hospitalization or death, all cause hospitalization, all-cause death, hospitalization for HF. In additional analyses, we will assess total healthcare resources utilization and cost.
• Data analysis plan:
  We compute incidence rates of outcomes per 1,000 person-years (pyrs) and use Cox regression to compute adjusted hazard ratios (aHRs). We apply propensity score balancing of potential confounders across the two treatment groups by inverse probability treatment weighting (IPTW), controlling age, gender, year of inclusion, diabetes duration, number of diabetes drugs used, metformin use, insulin use, diagnoses of retinopathy, neuropathy, or nephropathy, estimated glomerular filtration rate (eGFR), history of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, heart failure (further divided by duration and primary/secondary diagnosis), medical obesity, chronic obstructive pulmonary disease, cancer, use of angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs), other antihypertensives, statins, antiplatelet drugs, social and frailty markers, marital status, prescriptions for mental disorders, alcoholism, and prior admissions.