A Study to Observe the Effectiveness of Empagliflozin, Other SGLT-2 Inhibitors, or DPP-4 Inhibitors in Patients With Type 2 Diabetes

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 13 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor and Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitor
How many people: 327,624 participants
Where: 13 sitesin 11 countries
Study dates: 15 Apr 2019to 10 Dec 2021
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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.

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

13 sites in 11 countries.

Country

City, postcode or hospital

13 sites in 11 countries

Norway2 sites

Oslo University Hospital, Department of Clinical Lipidology
Oslo, 0424
Oslo University Hospital, Department of Cardiology
Oslo, 0450

Other trials in Norway

Sweden2 sites

TFS Trial Form Support International AB
Lund, 223 63
Quantify Research AB
Stockholm, 112 21

Other trials in Sweden

Denmark1 site

Steno Diabetes Center Copenhagen, Department of Clinical Epidemiology
Gentofte Municipality, 2820

Other trials in Denmark

Finland1 site

Helsinki University Hospital
Helsinki, 00029

Other trials in Finland

Germany1 site

University of Ulm, Institute for Epidemiology and medical biometry
Ulm, 89081

Other trials in Germany

Israel1 site

Maccabi Healthcare Services
Tel Aviv, 6812509

Other trials in Israel

Japan1 site

Gifu University
Gifu, 501-1193

Other trials in Japan

South Korea1 site

Ajou University Hospital
Suwon, 16499

Other trials in South Korea

Spain1 site

Instituto de Investigación Sanitaria INCLIVA
Valencia, 46010

Other trials in Spain

Taiwan1 site

Taiwan Society for Pharmacoeconomics and Outcome Research (TaSPOR)
Taipei, 100

Other trials in Taiwan

United Kingdom1 site

Leicester Real World Evidence Unit, Leicester general Hospital
Leicester, LE5 4PW

Other trials in United Kingdom

About this study

Official title: Multi-country Non-interventional Study on the Effectiveness of Empagliflozin in Adult Patients With Type 2 Diabetes in Europe and Asia.

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

Conditions: Diabetes Mellitus, Type 2
Being tested: Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor, Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitor
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitorDrug
Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor
Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitorDrug
Dipeptidyl peptidase-4 (DPP-4) inhibitor

Study groups in NCT03817463
Study group	Role	What they receive
New users of SGLT-2i		Patients with type 2 diabetes mellitus (T2DM), who were new users of any sodium-glucose cotransporter-2 inhibitors (SGLT-2i) including empagliflozin. Receives: Drug: Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor
New users of DPP-4i		Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 inhibitors (DPP-4i). Receives: Drug: Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition
Number of participants with Hospitalization for Heart Failure (HHF), using broad + specific HHF definition.
HHF - broad defined as any diagnosis associated with healthcare encounters, including hospitalizations and specialist outpatient and primary care encounters, or dispensation or any other record of the high-ceiling diuretics (loop diuretics).
HHF - specific defined as a primary diagnosis associated with hospital admission.
For HHF - broad + specific, HHF-specific definition was used unless only broad definition were available. However, for Japan South Korea and Taiwan, both definitions were available, but broad definition was used.
Measured: 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
Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition
Reported is the number of participants with hospitalization for heart failure (HHF), using broad definition of HHF.
HHF - broad is defined as any diagnosis associated with healthcare encounters, including hospitalizations and specialist outpatient and primary care encounters, or dispensation or any other record of the high-ceiling diuretics (loop diuretics).
Measured: 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
Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition
Reported is the number of participants with hospitalization for heart failure, using specific definition for HHF.
HHF - specific defined as a primary diagnosis associated with hospital admission.
Measured: 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
Number of Participants With All-cause Mortality (ACM)
Number of participants with all-cause mortality (ACM).
Measured: 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.
Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)
Number of participants with composite outcome, including hospitalization for heart failure (HHF) and all cause mortality (ACM).
Measured: 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.
Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)
Number of participants with composite outcome, including myocardial infraction (MI), stroke and all cause mortality (ACM).
Measured: 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.
Number of Participants With Myocardial Infarction (MI)
Number of participants with myocardial infarction (MI).
Measured: 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.
Number of Participants With Stroke
Number of participants with stroke.
Measured: 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 (19)

Number of Participants With Cardiovascular Mortality (CM)
Number of participants with cardiovascular mortality (CM).
Measured: 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.
Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality
Number of participants with composite outcome including hospitalization for heart failure (HHF) and cardiovascular (CV) mortality.
Measured: 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.
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
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.
Measured: 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.
Number of Participants With Coronary Revascularization Procedure
Number of participants with coronary revascularization procedure.
Measured: 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.
Number of Participants With End-stage Renal Disease (ESRD)
Number of participants with end-stage renal disease (ESRD).
Measured: 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.
Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline
Number of participants with estimated glomerular filtration rate (eGFR) decline.
Measured: 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.
Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria
Number of participants with progression from normoalbuminuria to micro- or macroalbuminuria.
Measured: 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.
Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria
Number of participants with composite outcome including Estimated glomerular filtration rate (eGFR) decline and progression to micro- or macroalbuminuria.
Measured: 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.
Number of Participants With Bone Fracture
Number of participants with bone fracture. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Measured: From index date until end of follow-up, up to 67 months.
Number of Participants With Diabetic Ketoacidosis
Number of participants with diabetic ketoacidosis. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i
Measured: From index date until end of follow-up, up to 67 months.
Number of Participants With Severe Hypoglycemia
Number of participants with severe hypoglycemia. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Measured: From index date until end of follow-up, up to 67 months.
Number of Participants With Lower-limb Amputation
Number of participants with lower-limb amputation. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Measured: From index date until end of follow-up, up to 67 months.
Number of Participants With Acute Kidney Injury Requiring Dialysis
Number of participants with acute kidney injury requiring dialysis. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Measured: From index date until end of follow-up, up to 67 months.
Healthcare Resource Utilization (HCRU): Number of Any Medical Visit
HCRU data were collected from seven of the 11 participating countries including Finland, Japan, South Korea, Norway, Spain, Sweden, and Taiwan. Outcomes captured as HCRU include emergency room visits, first inpatient stay, all-cause hospital admissions and outpatient healthcare visits.
HCRU outcomes were investigated for the matched cohort of empagliflozin/DPP-4 only. Due to possibly huge differences in healthcare systems and local practices, HCRU outcomes were presented descriptively by country as per prespecified analysis plan.
For arms with 0 patients analyzed, no data was collected for the specific outcome in this country.
Measured: From index date until end of follow-up, up to 67 months.
Healthcare Resource Utilization (HCRU): Number of Any Prescription
HCRU data were collected from seven of the 11 participating countries including Finland, Japan, South Korea, Norway, Spain, Sweden, and Taiwan. Outcomes captured as HCRU include pharmacy dispensations/prescriptions of different antidiabetic drugs, different drugs and prescriptions.
HCRU outcomes were investigated for the matched cohort of empagliflozin/DPP-4 only. Due to possibly huge differences in healthcare systems and local practices, HCRU outcomes were presented descriptively by country as per prespecified analysis plan.
For arms with 0 patients analyzed, no data was collected for the specific outcome in this country.
Measured: From index date until end of follow-up, up to 67 months.
Total Healthcare Costs - Finland, Norway, Sweden
Total healthcare cost include costs for emergency room visits, first inpatient stay, all-cause hospital admissions, outpatient healthcare visits and pharmacy dispensations/prescriptions of different antidiabetic drugs, different drugs and prescriptions. Total healthcare costs for Finland, Norway and Sweden are reported in Euro per year.
Due to possible huge differences in healthcare systems, cost of care outcomes are presented by country as prespecified in the analysis plan.
Measured: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - Japan
Total healthcare costs include costs for emergency room visits, first inpatient stay, all-cause hospital admissions, outpatient healthcare visits and pharmacy dispensations/prescriptions of different antidiabetic drugs, different drugs and prescriptions.
Total healthcare cost for Japan are reported in Japanese Yen (JPY) per year.
Due to possible huge differences in healthcare systems, cost of care outcomes are presented by country as prespecified in the analysis plan.
Measured: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - South Korea
Total healthcare costs include costs for emergency room visits, first inpatient stay, all-cause hospital admissions, outpatient healthcare visits and pharmacy dispensations/prescriptions of different antidiabetic drugs, different drugs and prescriptions.
Total healthcare costs for South Korea are reported in 1000 Korean Won (KRW) per year.
Due to possible huge differences in healthcare systems, cost of care outcomes are presented by country as prespecified in the analysis plan.
Measured: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - Taiwan
Total healthcare costs include costs for emergency room visits, first inpatient stay, all-cause hospital admissions, outpatient healthcare visits and pharmacy dispensations/prescriptions of different antidiabetic drugs, different drugs and prescriptions.
Total healthcare cost for Taiwan are reported in United States Dollar (USD) per year.
Due to possible huge differences in healthcare systems, cost of care outcomes are presented by country as prespecified in the analysis plan.
Measured: From index date until end of follow-up, up to 67 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Apr 201910 Dec 2021

First posted25 Jan 2019
Study start15 Apr 2019
Primary completion10 Dec 2021
Study completion10 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 327,624 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03817463
Sponsor's protocol ID: 1245-0195
Status last verified: May 2024
First submitted: 24 Jan 2019
Last updated: 23 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Publications

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.
PubMed 36097728

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Diabetes Mellitus, Type 2 trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multi-country Non-interventional Study on the Effectiveness of Empagliflozin in Adult Patients With Type 2 Diabetes in Europe and Asia.
ClinicalTrials.gov ID: NCT03817463
Acronym / sponsor ID: 1245-0195
Conditions: Diabetes Mellitus, Type 2
Study type: Observational
Recruitment status: Completed
Enrolment: 327,624 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 15 Apr 2019 (actual)
Primary completion: 10 Dec 2021 (actual)
Study completion: 10 Dec 2021 (actual)
First posted: 25 Jan 2019 (actual)
Results: Posted 23 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
New users of SGLT-2i	–	Drug: Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitorPatients with type 2 diabetes mellitus (T2DM), who were new users of any sodium-glucose cotransporter-2 inhibitors (SGLT-2i) including empagliflozin.
New users of DPP-4i	–	Drug: Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitorPatients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 inhibitors (DPP-4i).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
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.

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Subjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitorEmpagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor	Drug	New users of SGLT-2i
Subjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitorDipeptidyl peptidase-4 (DPP-4) inhibitor	Drug	New users of DPP-4i

Primary outcome

Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition
Time frame: 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
Number of participants with Hospitalization for Heart Failure (HHF), using broad + specific HHF definition. HHF - broad defined as any diagnosis associated with healthcare encounters, including hospitalizations and specialist outpatient and primary care encounters, or dispensation or any other record of the high-ceiling diuretics (loop diuretics). HHF - specific defined as a primary diagnosis associated with hospital admission. For HHF - broad + specific, HHF-specific definition was used unless only broad definition were available. However, for Japan South Korea and Taiwan, both definitions were available, but broad definition was used.
Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition
Time frame: 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
Reported is the number of participants with hospitalization for heart failure (HHF), using broad definition of HHF. HHF - broad is defined as any diagnosis associated with healthcare encounters, including hospitalizations and specialist outpatient and primary care encounters, or dispensation or any other record of the high-ceiling diuretics (loop diuretics).
Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition
Time frame: 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
Reported is the number of participants with hospitalization for heart failure, using specific definition for HHF. HHF - specific defined as a primary diagnosis associated with hospital admission.
Number of Participants With All-cause Mortality (ACM)
Time frame: 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.
Number of participants with all-cause mortality (ACM).
Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)
Time frame: 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.
Number of participants with composite outcome, including hospitalization for heart failure (HHF) and all cause mortality (ACM).
Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)
Time frame: 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.
Number of participants with composite outcome, including myocardial infraction (MI), stroke and all cause mortality (ACM).
Number of Participants With Myocardial Infarction (MI)
Time frame: 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.
Number of participants with myocardial infarction (MI).
Number of Participants With Stroke
Time frame: 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.
Number of participants with stroke.

19 secondary outcomes

Number of Participants With Cardiovascular Mortality (CM)
Time frame: 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.
Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality
Time frame: 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.
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
Time frame: 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.
Number of Participants With Coronary Revascularization Procedure
Time frame: 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.
Number of Participants With End-stage Renal Disease (ESRD)
Time frame: 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.
Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline
Time frame: 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.
Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria
Time frame: 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.
Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria
Time frame: 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.
Number of Participants With Bone Fracture
Time frame: From index date until end of follow-up, up to 67 months.
Number of Participants With Diabetic Ketoacidosis
Time frame: From index date until end of follow-up, up to 67 months.
Number of Participants With Severe Hypoglycemia
Time frame: From index date until end of follow-up, up to 67 months.
Number of Participants With Lower-limb Amputation
Time frame: From index date until end of follow-up, up to 67 months.
Number of Participants With Acute Kidney Injury Requiring Dialysis
Time frame: From index date until end of follow-up, up to 67 months.
Healthcare Resource Utilization (HCRU): Number of Any Medical Visit
Time frame: From index date until end of follow-up, up to 67 months.
Healthcare Resource Utilization (HCRU): Number of Any Prescription
Time frame: From index date until end of follow-up, up to 67 months.
Total Healthcare Costs - Finland, Norway, Sweden
Time frame: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - Japan
Time frame: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - South Korea
Time frame: From index date until end of follow-up, up to 67 months.
Total Healthcare Cost - Taiwan
Time frame: From index date until end of follow-up, up to 67 months.

Results and safety

Results posted to the registry on 23 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	163,812	163,812
DPP-4i (Matched to SGLT-2i)	163,812	163,812

Primary outcome: Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition

Time frame: 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. Count of participants. Unit: Participants

Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n = 163812	DPP-4i (Matched to SGLT-2i) n = 163812	Empagliflozin (Matched to DPP-4i) n = 85244	DPP-4i (Matched to Empagliflozin) n = 85244
Value	1395	2043	765	1083

Empagliflozin (Matched to DPP-4i) vs DPP-4i (Matched to Empagliflozin): Adjusted Hazard Ratio: 0.70 (95% CI 0.60 to 0.83), p <0.005, Cox proportional hazard model
SGLT-2i (Incl. Empa) (Matched to DPP-4i) vs DPP-4i (Matched to SGLT-2i): Adjusted Hazard Ratio: 0.66 (95% CI 0.57 to 0.78), p <0.005, Cox proportional hazard model

Population analysed: All patients included in the study, who were either new user of any SGLT-2i (incl. empagliflozin) or DPP-4i. Results are reported by 1:1 PS-matched cohorts of SGLT-2i/DPP-4i and empagliflozin/DPP-4i. Arms are not mutually exclusive.

Primary outcome: Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition

Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n = 163812	DPP-4i (Matched to SGLT-2i) n = 163812	Empagliflozin (Matched to DPP-4i) n = 85244	DPP-4i (Matched to Empagliflozin) n = 85244
Value	964	1260	514	641

SGLT-2i (Incl. Empa) (Matched to DPP-4i) vs DPP-4i (Matched to SGLT-2i): Ajusted hazard ratio: 0.75 (95% CI 0.69 to 0.81), p <0.005, Cox proportional hazard model
Empagliflozin (Matched to DPP-4i) vs DPP-4i (Matched to Empagliflozin): Ajusted hazard ratio: 0.78 (95% CI 0.69 to 0.88), p <0.005, Cox proportional hazard model

Primary outcome: Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition

Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n = 144306	DPP-4i (Matched to SGLT-2i) n = 144306	Empagliflozin (Matched to DPP-4i) n = 68087	DPP-4i (Matched to Empagliflozin) n = 68087
Denmark	273	345	178	195
Finnland	80	190	53	128
Germany	33	76	18	35
Israel	27	28	25	27
Japan	105	114	59	65
South Korea	12	19	–	–
Norway	49	124	23	63
Sweden	106	200	59	127

Empagliflozin (Matched to DPP-4i) vs DPP-4i (Matched to Empagliflozin): Adjusted Hazard Ratio: 0.68 (95% CI 0.56 to 0.83), p <0.005, Cox proportional hazard model
SGLT-2i (Incl. Empa) (Matched to DPP-4i) vs DPP-4i (Matched to SGLT-2i): Adjusted Hazard Ratio: 0.64 (95% CI 0.51 to 0.81), p <0.005, Cox proportional hazard model

Population analysed: Patients, who were either new user of any SGLT-2i (incl. empagliflozin) or DPP-4i. Results are reported by 1:1 PS-matched cohorts of SGLT-2i/DPP-4i and empagliflozin/DPP-4i. Arms are not mutually exclusive. Country-level results are reported and only include countries with non-missing data or a sufficient number of events to satisfy local patient privacy regulations.

Primary outcome: Number of Participants With All-cause Mortality (ACM)

Time frame: 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.. Count of participants. Unit: Participants

Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n = 163812	DPP-4i (Matched to SGLT-2i) n = 163812	Empagliflozin (Matched to DPP-4i) n = 85244	DPP-4i (Matched to Empagliflozin) n = 85244
Value	1371	2524	572	1177

Empagliflozin (Matched to DPP-4i) vs DPP-4i (Matched to Empagliflozin): Adjusted Hazard Ratio: 0.55 (95% CI 0.48 to 0.63), p <0.005, Cox proportional hazard model
SGLT-2i (Incl. Empa) (Matched to DPP-4i) vs DPP-4i (Matched to SGLT-2i): Adjusted Hazard Ratio: 0.59 (95% CI 0.54 to 0.65), p <0.005, Cox proportional hazard model

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Not applicable for serious and other adverse events. [All-cause mortality]: Up to 86 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	0 of 0	0 of 0	1,371 of 163,812
DPP-4i (Matched to SGLT-2i)	0 of 0	0 of 0	2,524 of 163,812

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36097728Nystrom 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.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Related trials for Diabetes Mellitus, Type 2

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kimberly G Brodovicz, (203) 448-1937 study chair

kimberly.brodovicz@boehringer-ingelheim.com

13 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 13 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Norway, Sweden, Denmark, Finland, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition (time frame: 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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03817463, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.