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
- Registration Number
- NCT02864914
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 333580
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Empagliflozin 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 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.
- Primary Outcome Measures
Name Time Method 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.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 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.
- Secondary Outcome Measures
Name Time Method 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.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.
Trial Locations
- Locations (1)
RTI health solutions
🇬🇧One Or Multiple Sites, United Kingdom