Diabetes Mellitus, Type 2
Conditions
Brief summary
Empagliflozin (Jardiance), a highly potent and selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2), was approved in Europe in May 2014 for the treatment of type 2 diabetes mellitus (T2DM) to improve glycaemic control in adults. As part of the risk management plan, Boehringer Ingelheim International GmbH (BI) has committed to conduct a post-authorisation safety study (PASS) to evaluate the liver and renal safety of empagliflozin. The study will also evaluate the risks of severe complications of urinary tract infections (UTIs) and genital infections. To evaluate the association between empagliflozin use and mentioned outcomes routinely collected health information from the Clinical Practice Research Datalink (CPRD), the Hospital Episodes Statistics, and Office of National Statistic will be used. This PASS will be conducted through an observational cohort study among adult patients with T2DM and at least 12 months of continuous enrolment in the CPRD where new users of empagliflozin will be compared to new users of dipeptidyl peptidase-4 (DPP4) inhibitors. Estimations will be made on the crude and adjusted incidence rates and adjusted incidence rate ratios of the primary and secondary outcomes.
Interventions
DRUGEmpagliflozin
drug
DRUGDPP-4 inhibitors
drug
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients will have T2DM, be initiating treatment with a study medication, and have at least 12 months of continuous registration in CPRD. * Further inclusion criteria apply
Exclusion criteria
* Patients will not have T1DM, will have no prior use of an SGLT2 inhibitor or DPP4 inhibitor, and will not be initiating a SGLT2-DPP4 fixed-dose combination. * Additional different
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rates of Genital Infections in Females (GIF) in Propensity Score-trimmed Cohort for GIF - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | up to 5 years | 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. |
| Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | up to 5 years | 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. |
| Incidence Rates of Severe Complications of Urinary Tract Infections (UTIs) in Propensity Score-trimmed Cohort for UTI - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Genital Infections in Males (GIM) in Propensity Score-trimmed Cohort for GIM - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 | up to 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Severe Genital Infections in Males (GIMH) in Propensity Score-trimmed Cohort for GIM - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only | up to 5 years | 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. |
| Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | up to 5 years | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Pre-assignment details
All subjects were screened for eligibility to ensure that they (the subjects) strictly met all inclusion and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 76,174 |
| 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. | 257,406 |
| Total | 333,580 |
Baseline characteristics
| Characteristic | Empagliflozin | DPP-4 Inhibitors | Total |
|---|---|---|---|
| Age, Continuous | 57.2 Years STANDARD_DEVIATION 10.8 | 62.1 Years STANDARD_DEVIATION 13.1 | 61.0 Years STANDARD_DEVIATION 12.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 30774 Participants | 110654 Participants | 141428 Participants |
| Sex: Female, Male Male | 45400 Participants | 146752 Participants | 192152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 4.64 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 3.41 Events per 1000 person-years |
| DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 2.60 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 10.96 Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 11.43 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 4.96 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 6.31 Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI | 16.89 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.41, 0.73]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.3, 0.55]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.45, 1.05]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.2, 0.86]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.56, 0.76]
Primary
Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1
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.
Time frame: up to 5 years
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | 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 |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 | 1.21 Events per 1000 person-years |
| DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 | 1.09 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 | NA Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 | 1.41 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.5, 1.19]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.23, 1.32]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.52, 1.41]
Primary
Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 2.57 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 1.50 Events per 1000 person-years |
| DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | NA Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 3.62 Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 0.92 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 0.70 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | NA Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA | 1.82 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [1.74, 2.76]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [1.77, 4.36]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [1.11, 4.12]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [1.48, 2.66]
Primary
Incidence Rates of Genital Infections in Females (GIF) in Propensity Score-trimmed Cohort for GIF - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Genital Infections in Females (GIF) in Propensity Score-trimmed Cohort for GIF - CPRD Only | 79.65 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Genital Infections in Females (GIF) in Propensity Score-trimmed Cohort for GIF - CPRD Only | 24.58 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [2.81, 3.74]
Primary
Incidence Rates of Genital Infections in Males (GIM) in Propensity Score-trimmed Cohort for GIM - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Genital Infections in Males (GIM) in Propensity Score-trimmed Cohort for GIM - CPRD Only | 47.23 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Genital Infections in Males (GIM) in Propensity Score-trimmed Cohort for GIM - CPRD Only | 11.70 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [3.46, 4.71]
Primary
Incidence Rates of Severe Complications of Urinary Tract Infections (UTIs) in Propensity Score-trimmed Cohort for UTI - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | 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 |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Severe Complications of Urinary Tract Infections (UTIs) in Propensity Score-trimmed Cohort for UTI - CPRD Only | 6.47 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.37, 0.72]
Secondary
Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | 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 |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | 1.23 Events per 1000 person-years |
| DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | NA Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | 4.19 Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | 2.67 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | 1.86 Events per 1000 person-years |
| DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | NA Events per 1000 person-years |
| DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) | Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2 | 5.47 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.56, 0.88]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.29, 0.85]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.34, 1.29]
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.61, 0.97]
Secondary
Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only | 9.32 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only | 17.73 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [0.43, 0.65]
Secondary
Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only | 58.42 Events per 1000 person-years |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only | 17.48 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [2.83, 3.95]
Secondary
Incidence Rates of Severe Genital Infections in Males (GIMH) in Propensity Score-trimmed Cohort for GIM - CPRD Only
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.
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin - CPRD (After Propensity Score Trimming) | 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 |
| Empagliflozin - HIRD (After Propensity Score Trimming) | Incidence Rates of Severe Genital Infections in Males (GIMH) in Propensity Score-trimmed Cohort for GIM - CPRD Only | 10.72 Events per 1000 person-years |
Comparison: Adjusted IR ratio was generated overall with corresponding 95% CIs 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.95% CI: [3.44, 4.75]