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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03817463

Enrollment

327624

Registered

2019-01-25

Start date

2019-04-15

Completion date

2021-12-10

Last updated

2024-09-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

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

Interventions

DRUGSubjects treated with Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor

Empagliflozin or any Sodium-glucose cotransporter-2 (SGLT-2) inhibitor

DRUGSubjects treated with Dipeptidyl peptidase-4 (DPP-4) inhibitor

Dipeptidyl peptidase-4 (DPP-4) inhibitor

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	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	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	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)	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)	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)	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)	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	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.

Secondary

Measure	Time frame	Description
Number of Participants With Bone Fracture	From index date until end of follow-up, up to 67 months.	Number of participants with bone fracture. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Number of Participants With Diabetic Ketoacidosis	From index date until end of follow-up, up to 67 months.	Number of participants with diabetic ketoacidosis. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i
Number of Participants With Severe Hypoglycemia	From index date until end of follow-up, up to 67 months.	Number of participants with severe hypoglycemia. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Number of Participants With Lower-limb Amputation	From index date until end of follow-up, up to 67 months.	Number of participants with lower-limb amputation. Data for this endpoint was only collected and analyzed for the matched cohort of empagliflozin/DPP-4i.
Number of Participants With Acute Kidney Injury Requiring Dialysis	From index date until end of follow-up, up to 67 months.	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.
Number of Participants With Cardiovascular Mortality (CM)	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 cardiovascular mortality (CM).
Healthcare Resource Utilization (HCRU): Number of Any Prescription	From index date until end of follow-up, up to 67 months.	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.
Total Healthcare Costs - Finland, Norway, Sweden	From index date until end of follow-up, up to 67 months.	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.
Total Healthcare Cost - Japan	From index date until end of follow-up, up to 67 months.	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.
Total Healthcare Cost - South Korea	From index date until end of follow-up, up to 67 months.	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.
Total Healthcare Cost - Taiwan	From index date until end of follow-up, up to 67 months.	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.
Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	From index date until end of follow-up, up to 67 months.	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.
Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality	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 3-point Major Adverse Cardiovascular (CV) Events (MACE), Defined as a Composite Outcome Including Myocardial Infarction (MI), Stroke and Cardiovascular (CV) Mortality	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 Coronary Revascularization Procedure	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 End-stage Renal Disease (ESRD)	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 Estimated Glomerular Filtration Rate (eGFR) Decline	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 Progression From Normoalbuminuria to Micro- or Macroalbuminuria	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 Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria	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 Estimated glomerular filtration rate (eGFR) decline and progression to micro- or macroalbuminuria.

Countries

Denmark, Finland, Germany, Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan, United Kingdom

Participant flow

Recruitment details

This was a non-interventional, multi-country study to compare the effectiveness and safety of empagliflozin in adult patients with type 2 diabetes. The study used secondary data sources from eleven countries, identifying new users of empagliflozin, any SGLT-2 inhibitor or any DPP4-inhibitor from May 2014 or November 2012 until December 2019.

Pre-assignment details

All subjects who strictly met all inclusion and none of the exclusion criteria where included in the study.

Participants by arm

Arm	Count
SGLT-2i (Incl. Empa) (Matched to DPP-4i) Patients with type 2 diabetes mellitus (T2DM), who were new users of any sodium-glucose cotransporter-2 inhibitors (SGLT-2i), including (incl.) new users of empagliflozin (empa). The study used secondary data sources from 11 countries (Denmark, Finland, Germany, Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan and the United Kingdom (UK CPRD, UK THIN) to identify new users of any SGLT-2i between November 2012 and December 2019. New user of any SGLT-2i were matched to new users of DPP-4i using a 1:1 propensity score (PS)-matching approach.	163,812
DPP-4i (Matched to SGLT-2i) Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 inhibitors (DPP-4i). The study used secondary data sources from 11 countries (Denmark, Finland, Germany, Israel, Japan, Norway, South Korea, Spain, Sweden, Taiwan and the United Kingdom (UK CPRD, UK THIN) to identify new users of DPP-4i between November 2012 and December 2019. New users of DPP-4i where matched to new users of any SGLT-2i using a 1:1 propensity score (PS)-matching approach.	163,812
Total	327,624

Baseline characteristics

Characteristic	SGLT-2i (Incl. Empa) (Matched to DPP-4i)	DPP-4i (Matched to SGLT-2i)	Total
Age, Continuous	60.02 Years STANDARD_DEVIATION 12.49	59.55 Years STANDARD_DEVIATION 12.49	59.56 Years STANDARD_DEVIATION 12.56
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	70990 Participants	71002 Participants	141992 Participants
Sex: Female, Male Male	92822 Participants	92810 Participants	185632 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1,371 / 163,812	2,524 / 163,812
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

Primary

Number of Participants With All-cause Mortality (ACM)

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With All-cause Mortality (ACM)	1371 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With All-cause Mortality (ACM)	2524 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With All-cause Mortality (ACM)	572 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With All-cause Mortality (ACM)	1177 Participants

p-value: <0.00595% CI: [0.48, 0.63]Cox proportional hazard model

p-value: <0.00595% CI: [0.54, 0.65]Cox proportional hazard model

Primary

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).

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)	2413 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)	3749 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)	1239 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Composite Outcome, Including Hospitalization for Heart Failure (HHF) and All Cause Mortality (ACM)	2063 Participants

p-value: <0.0595% CI: [0.56, 0.76]Cox proportional hazard model

p-value: <0.00595% CI: [0.61, 0.72]Cox proportional hazard model

Primary

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).

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)	2548 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)	3758 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)	1236 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)	1950 Participants

p-value: <0.00595% CI: [0.64, 0.82]Cox proportional hazard model

p-value: <0.00595% CI: [0.66, 0.78]Cox proportional hazard model

Primary

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).

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition	964 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition	1260 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition	514 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition	641 Participants

Comparison: HHF-broad.p-value: <0.00595% CI: [0.69, 0.81]Cox proportional hazard model

Comparison: HHF-broad.p-value: <0.00595% CI: [0.69, 0.88]Cox proportional hazard model

Primary

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	1395 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	2043 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	765 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	1083 Participants

Comparison: HHF-(broad+specific)p-value: <0.00595% CI: [0.6, 0.83]Cox proportional hazard model

Comparison: HHF-(broad + specific).p-value: <0.00595% CI: [0.57, 0.78]Cox proportional hazard model

Primary

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.

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

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Sweden	106 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Finnland	80 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Taiwan	60 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Denmark	273 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Germany	33 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Japan	105 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	South Korea	12 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Norway	49 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Israel	27 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Norway	124 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	South Korea	19 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Germany	76 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Israel	28 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Denmark	345 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Japan	114 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Sweden	200 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Taiwan	86 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Finnland	190 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Taiwan	29 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Sweden	59 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Germany	18 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Japan	59 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Israel	25 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Denmark	178 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Norway	23 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Finnland	53 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Taiwan	38 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Denmark	195 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Finnland	128 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Israel	27 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Japan	65 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Norway	63 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Sweden	127 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Hospitalization for Heart Failure (HHF), Specific Definition	Germany	35 Participants

Comparison: HHF-specific. Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.56, 0.83]Cox proportional hazard model

Comparison: HHF-specific. Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.51, 0.81]Cox proportional hazard model

Primary

Number of Participants With Myocardial Infarction (MI)

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Myocardial Infarction (MI)	701 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Myocardial Infarction (MI)	863 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Myocardial Infarction (MI)	364 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Myocardial Infarction (MI)	414 Participants

p-value: 0.81695% CI: [0.88, 1.18]Cox proportional hazard model

p-value: 0.01395% CI: [0.78, 0.97]Cox proportional hazard model

Primary

Number of Participants With Stroke

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.

Population: 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. 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Spain	49 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Denmark	183 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Japan	26 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	UK the Health Improvement Network databases (THIN)	17 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Norway	72 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	South Korea	107 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Taiwan	118 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Sweden	120 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Germany	6 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	UK Clinical Practice Research Datalink (CPRD)	42 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Israel	20 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Stroke	Finland	38 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Norway	87 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Denmark	230 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Finland	54 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Germany	24 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Israel	21 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Japan	50 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	South Korea	187 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Spain	53 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Sweden	134 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	Taiwan	104 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	UK Clinical Practice Research Datalink (CPRD)	39 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Stroke	UK the Health Improvement Network databases (THIN)	0 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Spain	15 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Taiwan	53 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Denmark	110 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Sweden	53 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	UK the Health Improvement Network databases (THIN)	7 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Israel	15 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	UK Clinical Practice Research Datalink (CPRD)	12 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	South Korea	43 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Finland	24 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Japan	12 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Stroke	Norway	28 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Israel	17 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Norway	36 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	UK Clinical Practice Research Datalink (CPRD)	12 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Spain	27 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Finland	40 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Sweden	102 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	UK the Health Improvement Network databases (THIN)	6 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Taiwan	53 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Denmark	112 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	Japan	13 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Stroke	South Korea	68 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.01195% CI: [0.71, 0.96]Cox proportional hazard model

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.06495% CI: [0.69, 1.01]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients in the study, who were included in the matched cohort of empagliflozin/DPP-4i from the following seven countries: Finland, Japan, South Korea, Norway, Spain, Sweden or Taiwan. HCRU outcomes are 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.

Arm	Measure	Group	Value (NUMBER)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	2607 Visit
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1472 Visit
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	1187 Visit
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	22232 Visit
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	38106 Visit
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	2138 Visit
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	5147 Visit
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	2294 Visit
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	42 Visit
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	27521 Visit
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	582 Visit
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	747 Visit
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	26095 Visit
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	43 Visit
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	704 Visit
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	1000 Visit
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	1499 Visit
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1008 Visit
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	117437 Visit
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	767 Visit
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	121503 Visit
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1266 Visit
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	847 Visit
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	2137 Visit
Empagliflozin (Matched to DPP-4) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	2191 Visit
Empagliflozin (Matched to DPP-4) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	885 Visit
Empagliflozin (Matched to DPP-4) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	19543 Visit
DPP-4 (Matched to Empagliflozin) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	25541 Visit
DPP-4 (Matched to Empagliflozin) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1169 Visit
DPP-4 (Matched to Empagliflozin) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	3368 Visit
Empagliflozin (Matched to DPP-4) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	441 Visit
Empagliflozin (Matched to DPP-4) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	178 Visit
Empagliflozin (Matched to DPP-4) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	6191 Visit
Empagliflozin (Matched to DPP-4) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	303 Visit
DPP-4 (Matched to Empagliflozin) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	228 Visit
DPP-4 (Matched to Empagliflozin) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	594 Visit
DPP-4 (Matched to Empagliflozin) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	6478 Visit
DPP-4 (Matched to Empagliflozin) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	365 Visit
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1401 Visit
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	17590 Visit
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	2413 Visit
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	1000 Visit
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	4310 Visit
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	27888 Visit
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	1613 Visit
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	2230 Visit
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1192 Visit
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	1620 Visit
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	2459 Visit
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	186380 Visit
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	All-caused hospital admissions	2029 Visit
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Outpatient healthcare visits	191095 Visit
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	First inpatient stay	1430 Visit
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Medical Visit	Emergency room visis	2834 Visit

Comparison: Emergency room visits - Finland95% CI: [0.69, 0.8]

Comparison: Emergency room visits - Japan95% CI: [0.59, 1.38]

Comparison: Emergency room visits - South Korea95% CI: [0.82, 1]

Comparison: Emergency room visit - Spain95% CI: [0.59, 0.87]

Comparison: Emergency room visit - Sweden95% CI: [0.87, 1.01]

Comparison: Emergency room visit - Taiwan95% CI: [0.8, 0.93]

Comparison: First impatient stay - Finland95% CI: [0.75, 0.85]

Comparison: First impatient stay - Japan95% CI: [0.68, 0.84]

Comparison: First impatient stay - South Korea95% CI: [0.69, 0.82]

Comparison: First impatient stay - Norway95% CI: [0.78, 0.94]

Comparison: First impatient stay - Spain95% CI: [0.66, 0.89]

Comparison: First impatient stay - Sweden95% CI: [0.81, 0.93]

Comparison: First impatient stay - Taiwan95% CI: [0.74, 0.86]

Comparison: All-cause hospital admissions95% CI: [0.64, 0.71]

Comparison: For all-cause hospital admissions - Japan95% CI: [0.63, 0.76]

Comparison: All-cause hospital admissions - South Korea95% CI: [0.66, 0.75]

Comparison: All-cause hospital admissions - Norway95% CI: [0.77, 0.85]

Comparison: All-cause hospital admissions - Spain95% CI: [0.6, 0.77]

Comparison: All-cause hospital admissions - Sweden95% CI: [0.8, 0.89]

Comparison: All-cause hospital admissions - Taiwan95% CI: [0.72, 0.87]

Comparison: Outpatient healthcare visits - Finland95% CI: [0.77, 0.79]

Comparison: Outpatient healthcare visits - Japan95% CI: [0.94, 0.97]

Comparison: Outpatient healthcare visits - South Korea95% CI: [0.96, 0.97]

Comparison: Outpatient healthcare visits - Norway95% CI: [0.94, 0.97]

Comparison: Outpatient healthcare visit - Spain95% CI: [0.85, 0.91]

Comparison: Outpatient healthcare visits - Sweden95% CI: [0.94, 0.98]

Comparison: Outpatient healthcare visits - Taiwan95% CI: [0.94, 1]

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Arm	Measure	Group	Value (NUMBER)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	259400 Prescription
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	80691 Prescription
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	341506 Prescription
DPP-4i (Matched to SGLT-2i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	96770 Prescription
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	41979 Prescription
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	11243 Prescription
Empagliflozin (Matched to DPP-4i)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	64297 Prescription
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	11003 Prescription
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	72589 Prescription
DPP-4i (Matched to Empagliflozin)	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	46888 Prescription
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	113596 Prescription
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	1417 Prescription
Empagliflozin (Matched to DPP-4) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	93395 Prescription
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	1639 Prescription
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	93602 Prescription
DPP-4 (Matched to Empagliflozin) - South Korea	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	114278 Prescription
Empagliflozin (Matched to DPP-4) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	53909 Prescription
Empagliflozin (Matched to DPP-4) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	174824 Prescription
DPP-4 (Matched to Empagliflozin) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	60072 Prescription
DPP-4 (Matched to Empagliflozin) - Norway	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	235661 Prescription
Empagliflozin (Matched to DPP-4) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	37679 Prescription
DPP-4 (Matched to Empagliflozin) - Spain	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	40448 Prescription
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	430360 Prescription
Empagliflozin (Matched to DPP-4) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	125423 Prescription
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	653294 Prescription
DPP-4 (Matched to Empagliflozin) - Sweden	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	151096 Prescription
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	32341 Prescription
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	188340 Prescription
Empagliflozin (Matched to DPP-4) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	207455 Prescription
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on prescriptions	208526 Prescription
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different antidiabetic drugs	29211 Prescription
DPP-4 (Matched to Empagliflozin) - Taiwan	Healthcare Resource Utilization (HCRU): Number of Any Prescription	Pharmacy dispensations/prescriptions based on different drugs	187291 Prescription

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - Spain95% CI: [0.84, 0.87]

Comparison: Pharmacy dispensations/prescriptions based on different antidiabetic drugs - Japan95% CI: [0.89, 0.94]

Comparison: Pharmacy dispensations/prescriptions based on different antidiabetic drugs - South Korea95% CI: [0.81, 0.93]

Comparison: Pharmacy dispensations/prescriptions based on different antidiabetic drugs - Taiwan95% CI: [1.08, 1.11]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - Finland95% CI: [1.1, 1.12]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - Japan95% CI: [0.81, 0.83]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - South Korea95% CI: [0.99, 1]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - Norway95% CI: [1.11, 1.14]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - Sweden95% CI: [1.25, 1.27]

Comparison: Pharmacy dispensations/prescriptions based on different drugs - Taiwan95% CI: [0.98, 1.02]

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - Finland95% CI: [1.01, 1.02]

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - Japan95% CI: [0.82, 0.84]

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - South Korea95% CI: [0.99, 1.01]

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - Norway95% CI: [0.92, 0.93]

Comparison: Pharmacy dispensations/prescriptions based on prescriptions - Sweden95% CI: [1, 1]

Secondary

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.

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to 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	843 Participants
DPP-4i (Matched to SGLT-2i)	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	1009 Participants
Empagliflozin (Matched to 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	393 Participants
DPP-4i (Matched to Empagliflozin)	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	516 Participants

p-value: 0.54595% CI: [0.81, 1.11]Cox proportional hazard model

p-value: 0.03695% CI: [0.83, 0.99]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients in the study, who were included in the 1:1 propensity-score matched cohort of empagliflozin/DPP-4i. 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Denmark	33 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Spain	21 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Taiwan	60 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Denmark	40 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Spain	46 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Acute Kidney Injury Requiring Dialysis	Taiwan	100 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.38, 0.82]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Finland	40 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Norway	23 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Japan	6 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Spain	19 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Israel	10 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Sweden	66 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	South Korea	41 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Taiwan	47 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Bone Fracture	Denmark	91 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Taiwan	50 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Denmark	88 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Finland	59 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Israel	6 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Japan	11 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	South Korea	50 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Norway	45 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Spain	20 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Bone Fracture	Sweden	98 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.09195% CI: [0.77, 1.02]Cox proportional hazard model

Secondary

Number of Participants With Cardiovascular Mortality (CM)

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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Taiwan	53 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Sweden	56 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Finland	67 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Norway	44 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Cardiovascular Mortality (CM)	Norway	73 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Cardiovascular Mortality (CM)	Finland	161 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Cardiovascular Mortality (CM)	Sweden	109 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Cardiovascular Mortality (CM)	Taiwan	76 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Sweden	24 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Taiwan	28 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Norway	17 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Cardiovascular Mortality (CM)	Finland	35 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Cardiovascular Mortality (CM)	Taiwan	29 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Cardiovascular Mortality (CM)	Finland	107 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Cardiovascular Mortality (CM)	Norway	32 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Cardiovascular Mortality (CM)	Sweden	80 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.42, 0.84]Cox proportional hazard model

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.49, 0.72]Cox proportional hazard model

Secondary

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.

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria	2456 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria	3652 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria	1324 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria	1710 Participants

p-value: 0.64295% CI: [0.73, 1.22]Cox proportional hazard model

p-value: 0.41795% CI: [0.66, 1.19]Cox proportional hazard model

Secondary

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.

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality	397 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality	806 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality	205 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality	505 Participants

p-value: <0.00595% CI: [0.46, 0.64]Cox proportional hazard model

p-value: <0.00595% CI: [0.47, 0.66]Cox proportional hazard model

Secondary

Number of Participants With Coronary Revascularization Procedure

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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Spain	0 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	UK Clinical Practice Research Datalink (CPRD)	61 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Germany	9 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Japan	268 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Sweden	212 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Finland	26 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Taiwan	296 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	South Korea	66 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Israel	124 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Denmark	173 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Norway	58 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Sweden	263 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Norway	64 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Finland	19 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Spain	7 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Denmark	184 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Germany	20 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Israel	103 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	UK Clinical Practice Research Datalink (CPRD)	73 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Taiwan	280 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	Japan	383 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Coronary Revascularization Procedure	South Korea	97 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	South Korea	23 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Denmark	117 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Finland	12 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Israel	111 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Japan	158 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Norway	10 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Sweden	115 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	Taiwan	140 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Coronary Revascularization Procedure	UK Clinical Practice Research Datalink (CPRD)	13 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Sweden	153 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Japan	206 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Israel	89 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	UK Clinical Practice Research Datalink (CPRD)	18 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Taiwan	152 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Finland	15 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Norway	11 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	South Korea	33 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Coronary Revascularization Procedure	Denmark	109 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.35395% CI: [0.79, 1.09]Cox proportional hazard model

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.19795% CI: [0.78, 1.05]Cox proportional hazard model

Secondary

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

Time frame: From index date until end of follow-up, up to 67 months.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Diabetic Ketoacidosis	Denmark	16 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Diabetic Ketoacidosis	Sweden	16 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Diabetic Ketoacidosis	Taiwan	19 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Diabetic Ketoacidosis	UK Health Improvement Network databases (THIN)	5 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Diabetic Ketoacidosis	UK Health Improvement Network databases (THIN)	0 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Diabetic Ketoacidosis	Denmark	6 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Diabetic Ketoacidosis	Taiwan	9 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Diabetic Ketoacidosis	Sweden	11 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [1.28, 3.03]Cox proportional hazard model

Secondary

Number of Participants With End-stage Renal Disease (ESRD)

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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Spain	0 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Japan	8 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	UK Health Improvement Network databases (THIN)	0 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	South Korea	0 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Finland	14 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Denmark	65 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Taiwan	38 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	UK Health Improvement Network databases (THIN)	5 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	Denmark	116 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	Finland	43 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	Japan	37 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	South Korea	21 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	Spain	9 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With End-stage Renal Disease (ESRD)	Taiwan	131 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	South Korea	0 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Spain	0 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Finland	8 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Denmark	34 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Taiwan	21 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With End-stage Renal Disease (ESRD)	Japan	6 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	Taiwan	52 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	South Korea	9 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	Finland	25 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	Denmark	56 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	Japan	17 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With End-stage Renal Disease (ESRD)	Spain	5 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.3, 0.63]Cox proportional hazard model

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: <0.00595% CI: [0.16, 0.44]Cox proportional hazard model

Secondary

Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline

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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline	1569 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline	1908 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline	914 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline	1043 Participants

p-value: 0.53595% CI: [0.89, 1.25]Cox proportional hazard model

p-value: 0.8595% CI: [0.84, 1.15]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Lower-limb Amputation	Denmark	9 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Lower-limb Amputation	Germany	12 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Lower-limb Amputation	Sweden	5 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Lower-limb Amputation	Taiwan	6 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Lower-limb Amputation	Taiwan	11 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Lower-limb Amputation	Denmark	8 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Lower-limb Amputation	Sweden	8 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Lower-limb Amputation	Germany	16 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.23395% CI: [0.52, 1.17]Cox proportional hazard model

Secondary

Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria

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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Sweden	297 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Clinical Practice Research Datalink (CPRD)	55 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Germany	260 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Israel	215 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Health Improvement Network databases (THIN)	15 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Sweden	401 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Clinical Practice Research Datalink (CPRD)	79 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Israel	213 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Germany	158 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Health Improvement Network databases (THIN)	24 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Sweden	149 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Germany	121 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Israel	165 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Clinical Practice Research Datalink (CPRD)	19 Participants
Empagliflozin (Matched to DPP-4i)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Finland	6 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	UK Clinical Practice Research Datalink (CPRD)	18 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Israel	149 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Germany	79 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Sweden	257 Participants
DPP-4i (Matched to Empagliflozin)	Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria	Finland	6 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.82895% CI: [0.81, 1.31]Cox proportional hazard model

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.94495% CI: [0.72, 1.42]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Denmark	29 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Finland	11 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Germany	16 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Israel	24 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	South Korea	12 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Spain	14 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Sweden	11 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	Taiwan	229 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	UK Clinical Practice Research Datalink (CPRD)	0 Participants
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Number of Participants With Severe Hypoglycemia	UK Health Improvement Network databases (THIN)	5 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Taiwan	294 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Denmark	23 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Spain	14 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Finland	13 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	UK Health Improvement Network databases (THIN)	9 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Germany	7 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Sweden	17 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	Israel	22 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	UK Clinical Practice Research Datalink (CPRD)	0 Participants
DPP-4i (Matched to SGLT-2i)	Number of Participants With Severe Hypoglycemia	South Korea	18 Participants

Comparison: Hazards ratios reported include data from all countries with non-missing values.p-value: 0.65495% CI: [0.75, 1.2]Cox proportional hazard model

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients who were included in the matched cohort of empagliflozin/DPP-4i from Japan. Costs are presented descriptively by country as per prespecified analysis plan.

Arm	Measure	Value (MEDIAN)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Total Healthcare Cost - Japan	91867 JPY per year
DPP-4i (Matched to SGLT-2i)	Total Healthcare Cost - Japan	63773 JPY per year

95% CI: [0.8, 0.88]

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients who were included in the matched cohort of empagliflozin/DPP-4i from Finland, Norway and Sweden. Cost are presented descriptively by country as per prespecified analysis plan.

Arm	Measure	Value (MEDIAN)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Total Healthcare Costs - Finland, Norway, Sweden	857 Euro per year
DPP-4i (Matched to SGLT-2i)	Total Healthcare Costs - Finland, Norway, Sweden	1356 Euro per year
Empagliflozin (Matched to DPP-4i)	Total Healthcare Costs - Finland, Norway, Sweden	1058 Euro per year
DPP-4i (Matched to Empagliflozin)	Total Healthcare Costs - Finland, Norway, Sweden	1336 Euro per year
Empagliflozin (Matched to DPP-4) - South Korea	Total Healthcare Costs - Finland, Norway, Sweden	658 Euro per year
DPP-4 (Matched to Empagliflozin) - South Korea	Total Healthcare Costs - Finland, Norway, Sweden	1036 Euro per year

Comparison: Total cost - Finland95% CI: [0.83, 0.94]

Comparison: Total costs - Norway95% CI: [0.86, 1.12]

Comparison: Total costs - Sweden95% CI: [0.92, 1.05]

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients who were included in the matched cohort of empagliflozin/DPP-4i from South Korea. Cost are presented descriptively by country as per prespecified analysis plan.

Arm	Measure	Value (MEDIAN)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Total Healthcare Cost - South Korea	214 1000 KRW per year
DPP-4i (Matched to SGLT-2i)	Total Healthcare Cost - South Korea	220 1000 KRW per year

Comparison: Total costs - South Korea95% CI: [0.34, 1.68]

Secondary

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.

Time frame: From index date until end of follow-up, up to 67 months.

Population: Only patients who were included in the matched cohort of empagliflozin/DPP-4i from Taiwan. Costs are presented descriptively by country as per prespecified analysis plan.

Arm	Measure	Value (MEDIAN)
SGLT-2i (Incl. Empa) (Matched to DPP-4i)	Total Healthcare Cost - Taiwan	530 USD per year
DPP-4i (Matched to SGLT-2i)	Total Healthcare Cost - Taiwan	431 USD per year

Comparison: Total costs - Taiwan95% CI: [0.92, 1.03]

Source: ClinicalTrials.gov · Data processed: Feb 11, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

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)

Number of Participants With Composite Outcome, Including Myocardial Infraction (MI), Stroke and All Cause Mortality (ACM)

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

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

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

Number of Participants With Myocardial Infarction (MI)

Number of Participants With Stroke

Healthcare Resource Utilization (HCRU): Number of Any Medical Visit

Healthcare Resource Utilization (HCRU): Number of Any Prescription

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 Acute Kidney Injury Requiring Dialysis

Number of Participants With Bone Fracture

Number of Participants With Cardiovascular Mortality (CM)

Number of Participants With Composite Outcome Including eGFR Decline and Progression to Micro- or Macroalbuminuria

Number of Participants With Composite Outcome Including Hospitalization for Heart Failure (HHF) and Cardiovascular (CV) Mortality

Number of Participants With Coronary Revascularization Procedure

Number of Participants With Diabetic Ketoacidosis

Number of Participants With End-stage Renal Disease (ESRD)

Number of Participants With Estimated Glomerular Filtration Rate (eGFR) Decline

Number of Participants With Lower-limb Amputation

Number of Participants With Progression From Normoalbuminuria to Micro- or Macroalbuminuria

Number of Participants With Severe Hypoglycemia

Total Healthcare Cost - Japan

Total Healthcare Costs - Finland, Norway, Sweden

Total Healthcare Cost - South Korea

Total Healthcare Cost - Taiwan