Trial Outcomes & Findings for A Study to Observe the Effectiveness of Empagliflozin, Other SGLT-2 Inhibitors, or DPP-4 Inhibitors in Patients With Type 2 Diabetes (NCT NCT03817463)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

327624 participants

Primary outcome timeframe

From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i

Results posted on

2024-09-23

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	163812	163812
Overall Study COMPLETED	163812	163812
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n=163812 Participants 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.	DPP-4i (Matched to SGLT-2i) n=163812 Participants 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.	Total n=327624 Participants Total of all reporting groups
Age, Continuous	60.02 Years STANDARD_DEVIATION 12.49 • n=163812 Participants	59.55 Years STANDARD_DEVIATION 12.49 • n=163812 Participants	59.56 Years STANDARD_DEVIATION 12.56 • n=327624 Participants
Sex: Female, Male Female	70990 Participants n=163812 Participants	71002 Participants n=163812 Participants	141992 Participants n=327624 Participants
Sex: Female, Male Male	92822 Participants n=163812 Participants	92810 Participants n=163812 Participants	185632 Participants n=327624 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i

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.

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.

Outcome measures

Outcome measures
Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n=163812 Participants 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.	DPP-4i (Matched to SGLT-2i) n=163812 Participants 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.	Empagliflozin (Matched to DPP-4i) n=85244 Participants Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, identified from secondary data sources from 11 countries. New users of empagliflozin were matched to new users of DPP-4i using a propensity score (PS)-matching approach.	DPP-4i (Matched to Empagliflozin) n=85244 Participants Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 inhibitors (DPP-4i) between May 2014 and December 2019, identified from secondary data sources from 11 countries. DPP-4 users were matched to new users of empagliflozin, using a 1:1 propensity score matching approach.	Empagliflozin (Matched to DPP-4) - South Korea Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only south-korean patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - South Korea Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only south-korean patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Norway Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only norwegian patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Norway Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only norwegian patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Spain Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only spanish patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Spain Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only spanish patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Sweden Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only swedish patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Sweden Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only swedish patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Taiwan Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only taiwanese patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Taiwan Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only taiwanese patients are included in this arm.
Number of Participants With Hospitalization for Heart Failure (HHF), Broad + Specific Definition	1395 Participants	2043 Participants	765 Participants	1083 Participants	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i

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.

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).

Outcome measures

Outcome measures
Measure	SGLT-2i (Incl. Empa) (Matched to DPP-4i) n=163812 Participants 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.	DPP-4i (Matched to SGLT-2i) n=163812 Participants 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.	Empagliflozin (Matched to DPP-4i) n=85244 Participants Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, identified from secondary data sources from 11 countries. New users of empagliflozin were matched to new users of DPP-4i using a propensity score (PS)-matching approach.	DPP-4i (Matched to Empagliflozin) n=85244 Participants Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 inhibitors (DPP-4i) between May 2014 and December 2019, identified from secondary data sources from 11 countries. DPP-4 users were matched to new users of empagliflozin, using a 1:1 propensity score matching approach.	Empagliflozin (Matched to DPP-4) - South Korea Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only south-korean patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - South Korea Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only south-korean patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Norway Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only norwegian patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Norway Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only norwegian patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Spain Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only spanish patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Spain Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only spanish patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Sweden Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only swedish patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Sweden Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only swedish patients are included in this arm.	Empagliflozin (Matched to DPP-4) - Taiwan Patients with type 2 diabetes mellitus (T2DM), who were new users of empagliflozin between May 2014 and December 2019, in all countries included in this study. Empagliflozin users were matched to incident users of (dipeptidyl peptidase-4) DPP-4 using a 1:1 propensity score matching approach. Only taiwanese patients are included in this arm.	DPP-4 (Matched to Empagliflozin) - Taiwan Patients with type 2 diabetes mellitus (T2DM), who were new users of dipeptidyl peptidase-4 (DPP-4) between May 2014 and December 2019, in all countries included in this study. DPP-4 users were matched to incident users of empagliflozin, using a 1:1 propensity score matching approach. Only taiwanese patients are included in this arm.
Number of Participants With Hospitalization for Heart Failure (HHF), Broad Definition	964 Participants	1260 Participants	514 Participants	641 Participants	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From index date until end of follow-up, up to 67 months for matched cohort of empagliflozin/DPP-4i. Up to 86 months for matched cohort of SGLT-2i/DPP-4i

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.

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.