Clinical trial NCT03817463: A Study to Observe the Effectiveness of Empagliflozin, Other SGLT-2 Inhibitors, or DPP-4 Inhibitors in Patients With Type 2 Diabetes
Official title: Multi-country Non-interventional Study on the Effectiveness of Empagliflozin in Adult Patients With Type 2 Diabetes in Europe and Asia.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-01-25
Enrollment: 327624
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This will be a non-interventional, multi-country cohort study using existing data and including adults (≥18 years) with a diagnosis of T2DM. All data will be obtained from electronically recorded longitudinal secondary data sources, separately in each included country. 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-4inhibitor.

Brief summary: Non-interventional, multi-country cohort study using existing data and including adults (≥18 years) with a diagnosis of Type 2 diabetes mellitus.


Eligibility criteria: Inclusion Criteria:

* Dispensation or any other record of empagliflozin, any SGLT-2 inhibitor, or any DPP-4 inhibitor use during the study period
* No dispensation or any other record of any other SGLT-2 inhibitor or DPP-4 inhibitor use during the preceding 12 months including at index date
* Having a diagnosis of T2DM before the index date, based on ICD-10 codes or other available data

Exclusion Criteria:

* Aged \<18 years on the first dispensation date or date of the first record of empagliflozin, any SGLT-2 inhibitor or any DPP-4 inhibitor use
* Type 1 diabetes mellitus
* Secondary diabetes
* Gestational diabetes
* Having a diagnosis of ESRD during the 12 months before the index date
* \<12 months of available data before the index date, and/or no complete history of drug dispensations/other records of the drug use during this period
* Missing or ambiguous data on age or sex

Primary outcomes:
measure: Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i
measure: Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i
measure: Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i
measure: Number of Participants With All-cause Mortality (ACM)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Myocardial Infarction (MI)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Stroke
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
Secondary outcomes:
measure: Number of Participants With Cardiovascular Mortality (CM)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With 3-point Major Adverse Cardiovascular (CV) Events (MACE), Defined as a Composite Outcome Including Myocardial Infarction (MI), Stroke and Cardiovascular (CV) Mortality
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Coronary Revascularization Procedure
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With End-stage Renal Disease (ESRD)
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria
timeFrame: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i.
measure: Number of Participants With Bone Fracture
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Number of Participants With Diabetic Ketoacidosis
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Number of Participants With Severe Hypoglycemia
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Number of Participants With Lower-limb Amputation
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Number of Participants With Acute Kidney Injury Requiring Dialysis
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Healthcare Resource Utilization (HCRU): Number of Any Medical Visit
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Healthcare Resource Utilization (HCRU): Number of Any Prescription
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Total Healthcare Costs - Finland, Norway, Sweden
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Total Healthcare Cost - Japan
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Total Healthcare Cost - South Korea
timeFrame: From index date until end of follow-up, up to 67 months.
measure: Total Healthcare Cost - Taiwan
timeFrame: From index date until end of follow-up, up to 67 months.
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen, Department of Clinical Epidemiology
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Ulm
country: Germany
facility: University of Ulm, Institute for Epidemiology and medical biometry
city: Tel Aviv
country: Israel
facility: Maccabi Healthcare Services
city: Gifu
country: Japan
facility: Gifu University
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, Department of Clinical Lipidology
city: Oslo
country: Norway
facility: Oslo University Hospital, Department of Cardiology
city: Valencia
country: Spain
facility: Instituto de Investigación Sanitaria INCLIVA
city: Lund
country: Sweden
facility: TFS Trial Form Support International AB
city: Stockholm
country: Sweden
facility: Quantify Research AB
city: Taipei City
country: Taiwan
facility: Taiwan Society for Pharmacoeconomics and Outcome Research (TaSPOR)
city: Leicester
country: United Kingdom
facility: Leicester Real World Evidence Unit, Leicester general Hospital
Study officials:
affiliation: kimberly.brodovicz@boehringer-ingelheim.com
name: Kimberly G Brodovicz, (203) 448-1937
role: STUDY_CHAIR
References:
citation: Nystrom T, Toresson Grip E, Gunnarsson J, Casajust P, Karlsdotter K, Skogsberg J, Ustyugova A; EMPRISE Study Group. Empagliflozin reduces cardiorenal events, healthcare resource use and mortality in Sweden compared to dipeptidyl peptidase-4 inhibitors: Real world evidence from the Nordic EMPRISE study. Diabetes Obes Metab. 2023 Jan;25(1):261-271. doi: 10.1111/dom.14870. Epub 2022 Oct 10.