Trial Outcomes & Findings for Post-authorisation Safety Study in Patients With Type 2 Diabetes to Assess the Risk of Liver Injury, Kidney Injury, Urinary Tract and Genital Infections, and Diabetic Ketoacidosis in Patients Treated With Empagliflozin, Compared to DPP-4 Inhibitors (NCT NCT02864914)
NCT ID: NCT02864914
Last Updated: 2024-11-15
Results Overview
Incidence rates (IRs) of acute liver injury (ALI) in patients with no predisposing conditions (ALI1) in propensity score-trimmed study cohorts for ALI1 are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% confidence interval (CIs) were generated using a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
COMPLETED
333580 participants
up to 5 years
2024-11-15
Participant Flow
This was a non-interventional observational cohort study using existing data from routine medical care in the Clinical Practice Research Datalink in the United Kingdom, the Danish Population Registries in Denmark, and the HealthCore Integrated Research Database in the United States investigating safety among patients with type 2 diabetes mellitus treated with empagliflozin versus Dipeptidyl peptidase-4 inhibitors.
All subjects were screened for eligibility to ensure that they (the subjects) strictly met all inclusion and none of the exclusion criteria.
Participant milestones
| Measure |
Empagliflozin
All eligible patients type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, from existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK), HealthCore Integrated Research Database (HIRD) in the United States (US), and Danish Population Registries (Danish Registries) in Denmark.
The study period started on 01 August 2014, the date of empagliflozin launch in the UK, US, and Denmark. The study end date was 01 August 2019 in CPRD and Danish Registries and 31 July 2019 in HIRD.
|
DPP-4 Inhibitors
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK), HealthCore Integrated Research Database (HIRD) in the United States (US), and Danish Population Registries (Danish Registries) in Denmark.
The study period started on 01 August 2014, the date of empagliflozin launch in the UK, US, and Denmark. The study end date was 01 August 2019 in CPRD and Danish Registries and 31 July 2019 in HIRD.
|
|---|---|---|
|
Overall Study
STARTED
|
76174
|
257406
|
|
Overall Study
Propensity Score-trimmed Cohort for DKA
|
64599
|
203315
|
|
Overall Study
Propensity Score-trimmed Cohort for AKI
|
58393
|
167823
|
|
Overall Study
Propensity Score-trimmed Cohort for ALI2
|
62917
|
197172
|
|
Overall Study
Propensity Score-trimmed Cohort for CKD - CPRD Only
|
13256
|
62435
|
|
Overall Study
Propensity Score-trimmed Cohort for GIM - CPRD Only
|
8272
|
45683
|
|
Overall Study
Propensity Score-trimmed Cohort for UTI - CPRD Only
|
14050
|
77330
|
|
Overall Study
Propensity Score-trimmed Cohort for GIF - CPRD Only
|
5802
|
31904
|
|
Overall Study
Propensity Score-trimmed Cohort for ALI1
|
36053
|
154554
|
|
Overall Study
COMPLETED
|
76174
|
257406
|
|
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
| Measure |
Empagliflozin
n=76174 Participants
All eligible patients type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, from existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK), HealthCore Integrated Research Database (HIRD) in the United States (US), and Danish Population Registries (Danish Registries) in Denmark.
The study period started on 01 August 2014, the date of empagliflozin launch in the UK, US, and Denmark. The study end date was 01 August 2019 in CPRD and Danish Registries and 31 July 2019 in HIRD.
|
DPP-4 Inhibitors
n=257406 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK), HealthCore Integrated Research Database (HIRD) in the United States (US), and Danish Population Registries (Danish Registries) in Denmark.
The study period started on 01 August 2014, the date of empagliflozin launch in the UK, US, and Denmark. The study end date was 01 August 2019 in CPRD and Danish Registries and 31 July 2019 in HIRD.
|
Total
n=333580 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.2 Years
STANDARD_DEVIATION 10.8 • n=76174 Participants
|
62.1 Years
STANDARD_DEVIATION 13.1 • n=257406 Participants
|
61.0 Years
STANDARD_DEVIATION 12.6 • n=333580 Participants
|
|
Sex: Female, Male
Female
|
30774 Participants
n=76174 Participants
|
110654 Participants
n=257406 Participants
|
141428 Participants
n=333580 Participants
|
|
Sex: Female, Male
Male
|
45400 Participants
n=76174 Participants
|
146752 Participants
n=257406 Participants
|
192152 Participants
n=333580 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria, and with non-missing ALI results and with no predisposing conditions (ALI1) were included. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A ALI1-specific propensity score model was used for the propensity score including all ALI1-related variables. Due to the Danish small cell count policy, some cohorts were not reported (see limits \& caveats).
Incidence rates (IRs) of acute liver injury (ALI) in patients with no predisposing conditions (ALI1) in propensity score-trimmed study cohorts for ALI1 are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% confidence interval (CIs) were generated using a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=11189 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=24864 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
n=61254 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=27404 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=65896 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1
|
0.60 Events per 1000 person-years
Interval 0.27 to 1.36
|
1.21 Events per 1000 person-years
Interval 0.79 to 1.86
|
1.09 Events per 1000 person-years
Interval 0.75 to 1.59
|
NA Events per 1000 person-years
Due to the low number of events, the Poisson regression models had convergence/validity issues. Therefore, results were reported as "not estimable".
|
1.41 Events per 1000 person-years
Interval 1.04 to 1.92
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A AKI-specific propensity score model was used for the propensity score including all AKI-related variables.
Incidence rates (IRs) of acute kidney injury (AKI) in propensity score-trimmed cohort for AKI are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=13215 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=9296 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
n=5362 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=30520 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=61879 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=28897 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=2297 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=74750 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI
|
4.64 Events per 1000 person-years
Interval 3.51 to 6.12
|
3.41 Events per 1000 person-years
Interval 2.31 to 5.02
|
2.60 Events per 1000 person-years
Interval 1.54 to 4.4
|
10.96 Events per 1000 person-years
Interval 9.61 to 12.49
|
11.43 Events per 1000 person-years
Interval 10.21 to 12.79
|
4.96 Events per 1000 person-years
Interval 4.17 to 5.89
|
6.31 Events per 1000 person-years
Interval 3.4 to 11.71
|
16.89 Events per 1000 person-years
Interval 15.56 to 18.33
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A DKA-specific propensity score model was used for the propensity score including all DKA-related variables.
Incidence rates (IRs) of diabetic ketoacidosis (DKA) in propensity score-trimmed cohort for DKA are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=14086 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=9923 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
n=5905 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=34685 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=77408 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=33973 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=2742 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=89192 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA
|
2.57 Events per 1000 person-years
Interval 1.78 to 3.7
|
1.50 Events per 1000 person-years
Interval 0.85 to 2.64
|
NA Events per 1000 person-years
Due to the low number of events, the Poisson regression models had convergence/validity issues. Therefore, results were reported as "not estimable".
|
3.62 Events per 1000 person-years
Interval 2.93 to 4.48
|
0.92 Events per 1000 person-years
Interval 0.67 to 1.28
|
0.70 Events per 1000 person-years
Interval 0.46 to 1.07
|
NA Events per 1000 person-years
Due to the low number of events, the Poisson regression models had convergence/validity issues. Therefore, results were reported as "not estimable".
|
1.82 Events per 1000 person-years
Interval 1.47 to 2.26
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A UTI-specific propensity score model was used for the propensity score including all UTI-related variables. Because UTI was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of severe complications of urinary tract infections (UTIs) in propensity score-trimmed cohort for UTI among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=14050 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=77330 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Severe Complications of Urinary Tract Infections (UTIs) in Propensity Score-trimmed Cohort for UTI - CPRD Only
|
3.32 Events per 1000 person-years
Interval 2.42 to 4.54
|
6.47 Events per 1000 person-years
Interval 5.64 to 7.42
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A GIM-specific propensity score model was used for the propensity score including all GIM-related variables. Because genital infection was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of genital infections in males (GIM) in propensity score-trimmed cohorts for GIM among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=8272 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=45683 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Genital Infections in Males (GIM) in Propensity Score-trimmed Cohort for GIM - CPRD Only
|
47.23 Events per 1000 person-years
Interval 42.28 to 52.76
|
11.70 Events per 1000 person-years
Interval 10.45 to 13.1
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A GIF-specific propensity score model was used for the propensity score including all GIF-related variables. Because genital infection was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of genital infections in females (GIF) in propensity score-trimmed cohort for GIF among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=5802 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=31940 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Genital Infections in Females (GIF) in Propensity Score-trimmed Cohort for GIF - CPRD Only
|
79.65 Events per 1000 person-years
Interval 71.72 to 88.45
|
24.58 Events per 1000 person-years
Interval 22.28 to 27.13
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A ALI2-specific propensity score model was used for the propensity score including all ALI2-related variables.
Incidence rates (IRs) of acute liver injury (ALI) in patients with or without predisposing conditions (ALI2) in propensity score-trimmed cohort for ALI2 are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=13913 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=9681 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
n=5740 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=33583 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=75580 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=33308 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
n=2661 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
n=85623 Participants
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2
|
1.33 Events per 1000 person-years
Interval 0.81 to 2.19
|
1.23 Events per 1000 person-years
Interval 0.66 to 2.31
|
NA Events per 1000 person-years
Due to the low number of events, the Poisson regression models had convergence/validity issues. Therefore, results were reported as "not estimable".
|
4.19 Events per 1000 person-years
Interval 3.43 to 5.11
|
2.67 Events per 1000 person-years
Interval 2.14 to 3.33
|
1.86 Events per 1000 person-years
Interval 1.43 to 2.41
|
NA Events per 1000 person-years
Due to the low number of events, the Poisson regression models had convergence/validity issues. Therefore, results were reported as "not estimable".
|
5.47 Events per 1000 person-years
Interval 4.79 to 6.26
|
SECONDARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A CKD-specific propensity score model was used for the propensity score including all CKD-related variables. Because CKD was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of chronic kidney disease (CKD) in propensity score-trimmed cohort for CKD among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=13256 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=62435 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only
|
9.32 Events per 1000 person-years
Interval 7.68 to 11.31
|
17.73 Events per 1000 person-years
Interval 16.16 to 19.45
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A GIM-specific propensity score model was used for the propensity score including all GIM-related variables. Because genital infection was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of severe genital infections in males (GIMH) in propensity score-trimmed cohort for GIM among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=8272 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=45683 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
|---|---|---|---|---|---|---|---|---|
|
Incidence Rates of Severe Genital Infections in Males (GIMH) in Propensity Score-trimmed Cohort for GIM - CPRD Only
|
43.35 Events per 1000 person-years
Interval 38.63 to 48.65
|
10.72 Events per 1000 person-years
Interval 9.53 to 12.07
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 5 yearsPopulation: All eligible subjects who strictly met all inclusion and none of the exclusion criteria. The cohort after propensity score trimming (extreme values of propensity score were trimmed) was used. A GIF-specific propensity score model was used for the propensity score including all GIF-related variables. Because genital infection was evaluated only in CPRD database, only participants from CPRD were used.
Incidence rates (IRs) of severe genital infections in females (GIFH) in propensity score-trimmed cohort for GIF among CPRD participants are reported. Unadjusted IRs were computed as the number of events divided by the total person-years at risk in the empagliflozin and DPP-4 inhibitors cohorts overall and for subgroups with and without insulin use at the index date. IRs adjusted for propensity score decile were generated for empagliflozin and DPP-4 inhibitor cohorts overall (not stratified by any other variable). These estimates with corresponding 95% CIs were generated through the application of a Poisson regression model where the outcome was modelled as a function of treatment cohort (empagliflozin or DPP-4 inhibitors) and propensity score decile (specified as a categorical variable) with the log of time of exposure (in years) as the offset. If any variable remained unbalanced after trimming, it was added as an independent variable in the Poisson regression model.
Outcome measures
| Measure |
Empagliflozin - CPRD (After Propensity Score Trimming)
n=5802 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
Empagliflozin - HIRD (After Propensity Score Trimming)
n=31940 Participants
All eligible patients with type 2 diabetes mellitus initiating Empagliflozin treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating Empagliflozin after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - CPRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (UK).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
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DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with \<3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
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DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period with ≥3 glucose-lowering drugs, existing data of routine medical care in the Danish Population Registries (Danish Registries) in Denmark.
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
|
DPP-4 Inhibitors - HIRD (After Propensity Score Trimming)
All eligible patients with type 2 diabetes mellitus initiating Dipeptidyl peptidase-4 (DPP-4) inhibitors treatment within the study period, existing data of routine medical care in the HealthCore Integrated Research Database (HIRD) in the United States (US).
This group includes all eligible participants initiating DPP-4 inhibitors after propensity score-trimming, where the model used for propensity score was endpoint-specific including all variables related to the endpoint.
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Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only
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58.42 Events per 1000 person-years
Interval 51.73 to 65.97
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17.48 Events per 1000 person-years
Interval 15.57 to 19.64
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Adverse Events
Empagliflozin
DPP-4 Inhibitors
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER