Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)

Data collection methods

Combined primary data collection and secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Study drug International non-proprietary name (INN) or common name

EMPAGLIFLOZIN
DAPAGLIFLOZIN
CANAGLIFLOZIN
ERTUGLIFLOZIN
SITAGLIPTIN
VILDAGLIPTIN
SAXAGLIPTIN
ALOGLIPTIN
LINAGLIPTIN
METFORMIN

Medical condition to be studied

Type 2 diabetes mellitus
Population studied

Short description of the study population

Adult patients aged 18 years or older diagnosed with type 2 diabetes mellitus (T2DM) identified from Denmark, Finland, Germany, Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan, and the United Kingdom. The study population consisted of 3 sub-cohorts included patients with empagliflozin use, any SGLT-2 inhibitor use, and any DPP-4 inhibitor use.
Inclusion criteria:
- Dispensation or any other record of empagliflozin, any SGLT2i, or any DPP4i use during the study period,
- No dispensation or any other record of any other SGLT2i or DPP4i use during the 12 months preceding the index date, and
- Having a diagnosis of T2DM before the index date, based on codes from the 10th revision (ICD-10) of the International Classification of Diseases and Related Health Problems (ICD) or other available data.
- For the Nordic countries, history of metformin prescription at any time in the past was also an additional inclusion criterion.

Exclusion criteria:
- Aged <18 years on the first dispensation date or date of the first record of empagliflozin, any SGLT2i or any DPP-4 inhibitor use,
- Pre-existing diagnosis of T1DM during the 12 months before the index date,
- Pre-existing diagnosis of secondary diabetes or gestational diabetes in the 12 months prior to the index date
- Having a diagnosis of ESRD during the 12 months before the index date,
- <12 months of available data before the index date (less than 6 months for Germany), and/or no complete history of drug dispensations/other records of
drug use during this period, or missing or ambiguous data on age or sex

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 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

Patients with type 2 diabetes

Estimated number of subjects

150000
Study design details

Main study objective

The overall objective of this study is to examine effectiveness, safety, health care resource utilization, and cost of care outcomes associated with the use of empagliflozin or any SGLT-2 inhibitors, compared with use of dipeptidyl peptidase-4 (DPP-4) inhibitors, among patients with T2DM.

Outcomes

Secondary objectives are related to cardiovascular and renal effectiveness, safety, healthcare resource utilization and cost of care. Secondary objectives related to effectiveness are to examine the risk of coronary revascularization procedures, end-stage renal disease, cardiovascular mortality, and two composite outcomes: one including hospitalization for heart failure and cardiovascular mortality and another including MI, stroke, and cardiovascular mortality (MACE) and examine healthcare resource utilization and cost of care.

Data analysis plan

Individual level data will be analyzed in countries. To meet the objectives of the multi-country study, aggregate-level results obtained from the countries will be combined: effectiveness and safety results will be pooled in a meta-analysis, while HCRU and cost of care results will be combined descriptively. In each country, patients initiating treatment with empagliflozin or any other SGLT- 2 inhibitor will be compared with PS-matched patients initiating treatment with any DPP-4 inhibitor. Pairwise PS models will be estimated using logistic regression including appropriate covariates. The primary and secondary effectiveness outcomes and safety outcomes will be analyzed and compared across subcohorts by incidence rates, cumulative-incidence plots, and Cox proportional hazards models. For secondary outcomes on healthcare resource utilization and cost of care, number of visits, inpatient days, dispensations and amount of costs will be determined during follow-up.