Diabetes Mellitus, Type 2NCT02864914

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

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Empagliflozin and DPP-4 inhibitors
How many people: 333,580 participants
Where: 1 siteUnited Kingdom
Study dates: 15 Mar 2016to 29 Jul 2022
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: T2DM eligible patients in CPRD

Who may be able to join

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

Who cannot join

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 exclusion criteria will be applied according to each outcomes of interest.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

RTI health solutions
One Or Multiple Sites

Other trials in United Kingdom

About this study

Official title: Post-authorisation Safety Study in Patients With Type 2 Diabetes Mellitus to Assess the Risk of Acute Liver Injury, Acute Kidney Injury and Chronic Kidney Disease, Severe Complications of Urinary Tract Infection, Genital Infections, and Diabetic Ketoacidosis Among Patients Treated With Empagliflozin Compared to Patients Treated With DPP-4 Inhibitors

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.

Conditions: Diabetes Mellitus, Type 2
Being tested: Empagliflozin, DPP-4 inhibitors
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EmpagliflozinDrug
drug
DPP-4 inhibitorsDrug
drug

Study groups in NCT02864914
Study group	Role	What they receive
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. Receives: Drug: Empagliflozin
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. Receives: Drug: DPP-4 inhibitors

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years

Secondary outcomes (4)

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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years
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.
Measured: up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 201629 Jul 2022

First posted12 Aug 2016 (estimated)
Study start15 Mar 2016
Primary completion29 Jul 2022
Study completion29 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 333,580 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02864914
Sponsor's protocol ID: 1245.96
Status last verified: Sep 2024
First submitted: 13 May 2016
Last updated: 15 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Post-authorisation Safety Study in Patients With Type 2 Diabetes Mellitus to Assess the Risk of Acute Liver Injury, Acute Kidney Injury and Chronic Kidney Disease, Severe Complications of Urinary Tract Infection, Genital Infections, and Diabetic Ketoacidosis Among Patients Treated With Empagliflozin Compared to Patients Treated With DPP-4 Inhibitors
ClinicalTrials.gov ID: NCT02864914
Acronym / sponsor ID: 1245.96
Conditions: Diabetes Mellitus, Type 2
Study type: Observational
Recruitment status: Completed
Enrolment: 333,580 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: 15 Mar 2016 (actual)
Primary completion: 29 Jul 2022 (actual)
Study completion: 29 Jul 2022 (actual)
First posted: 12 Aug 2016 (estimated)
Results: Posted 15 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
Empagliflozin	–	Drug: EmpagliflozinAll 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	–	Drug: DPP-4 inhibitorsAll 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: T2DM eligible patients in CPRD

Key inclusion criteria (2 listed)

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

Key exclusion criteria (2 listed)

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 exclusion criteria will be applied according to each outcomes of interest.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Empagliflozindrug	Drug	Empagliflozin
DPP-4 inhibitorsdrug	Drug	DPP-4 inhibitors

Primary outcome

Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.

4 secondary outcomes

Incidence Rates of Acute Liver Injury (ALI) in Patients With or Without Predisposing Conditions (ALI2) in Propensity Score-trimmed Cohort for ALI2
Time frame: up to 5 years
Incidence Rates of Chronic Kidney Disease (CKD) in Propensity Score-trimmed Cohort for CKD - CPRD Only
Time frame: up to 5 years
Incidence Rates of Severe Genital Infections in Males (GIMH) in Propensity Score-trimmed Cohort for GIM - CPRD Only
Time frame: up to 5 years
Incidence Rates of Severe Genital Infections in Females (GIFH) in Propensity Score-trimmed Cohort for GIF - CPRD Only
Time frame: up to 5 years

Results and safety

Results posted to the registry on 15 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Empagliflozin	76,174	76,174
DPP-4 Inhibitors	257,406	257,406

Primary outcome: Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1

Time frame: up to 5 years. Number (95% Confidence Interval). Unit: Events per 1000 person-years

Measure	Empagliflozin - CPRD (After Propensity Score Trimming) n = 11189	Empagliflozin - HIRD (After Propensity Score Trimming) n = 24864	DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) n = 61254	DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 27404	DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) n = 65896
Value	0.60 (0.27 to 1.36)	1.21 (0.79 to 1.86)	1.09 (0.75 to 1.59)	NA (NA to NA)	1.41 (1.04 to 1.92)

Empagliflozin - CPRD (After Propensity Score Trimming) vs Empagliflozin - HIRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - HIRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.77 (95% CI 0.50 to 1.19)
Empagliflozin - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.55 (95% CI 0.23 to 1.32)
Empagliflozin - HIRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - HIRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.86 (95% CI 0.52 to 1.41)

Population analysed: 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).

Primary outcome: Incidence Rates of Acute Kidney Injury (AKI) in Propensity Score-trimmed Cohort for AKI

Time frame: up to 5 years. Number (95% Confidence Interval). Unit: Events per 1000 person-years

Measure	Empagliflozin - CPRD (After Propensity Score Trimming) n = 13215	Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 9296	Empagliflozin - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 5362	Empagliflozin - HIRD (After Propensity Score Trimming) n = 30520	DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) n = 61879	DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 28897	DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 2297	DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) n = 74750
Value	4.64 (3.51 to 6.12)	3.41 (2.31 to 5.02)	2.60 (1.54 to 4.40)	10.96 (9.61 to 12.49)	11.43 (10.21 to 12.79)	4.96 (4.17 to 5.89)	6.31 (3.40 to 11.71)	16.89 (15.56 to 18.33)

Empagliflozin - CPRD (After Propensity Score Trimming) vs Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs Empagliflozin - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) vs Empagliflozin - HIRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) vs DPP-4 Inhibitors - HIRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.54 (95% CI 0.41 to 0.73)
Empagliflozin - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.41 (95% CI 0.30 to 0.55)
Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.69 (95% CI 0.45 to 1.05)

Primary outcome: Incidence Rates of Diabetic Ketoacidosis (DKA) in Propensity Score-trimmed Cohort for DKA

Time frame: up to 5 years. Number (95% Confidence Interval). Unit: Events per 1000 person-years

Measure	Empagliflozin - CPRD (After Propensity Score Trimming) n = 14086	Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 9923	Empagliflozin - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 5905	Empagliflozin - HIRD (After Propensity Score Trimming) n = 34685	DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) n = 77408	DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 33973	DPP-4 Inhibitors - Danish Registries ≥3 Glucose-lowering Drugs (After Propensity Score Trimming) n = 2742	DPP-4 Inhibitors - HIRD (After Propensity Score Trimming) n = 89192
Value	2.57 (1.78 to 3.70)	1.50 (0.85 to 2.64)	NA (NA to NA)	3.62 (2.93 to 4.48)	0.92 (0.67 to 1.28)	0.70 (0.46 to 1.07)	NA (NA to NA)	1.82 (1.47 to 2.26)

Empagliflozin - CPRD (After Propensity Score Trimming) vs Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs Empagliflozin - HIRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs DPP-4 Inhibitors - HIRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 2.19 (95% CI 1.74 to 2.76)
Empagliflozin - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 2.78 (95% CI 1.77 to 4.36)
Empagliflozin - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming) vs DPP-4 Inhibitors - Danish Registries <3 Glucose-lowering Drugs (After Propensity Score Trimming): Adjusted incidence rate ratio: 2.14 (95% CI 1.11 to 4.12)

Population analysed: 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.

Primary outcome: Incidence Rates of Severe Complications of Urinary Tract Infections (UTIs) in Propensity Score-trimmed Cohort for UTI - CPRD Only

Time frame: up to 5 years. Number (95% Confidence Interval). Unit: Events per 1000 person-years

Measure	Empagliflozin - CPRD (After Propensity Score Trimming) n = 14050	DPP-4 Inhibitors - CPRD (After Propensity Score Trimming) n = 77330
Value	3.32 (2.42 to 4.54)	6.47 (5.64 to 7.42)

Empagliflozin - CPRD (After Propensity Score Trimming) vs DPP-4 Inhibitors - CPRD (After Propensity Score Trimming): Adjusted incidence rate ratio: 0.51 (95% CI 0.37 to 0.72)

Population analysed: 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.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: No applicable.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Empagliflozin	0 of 0	0 of 0	0
DPP-4 Inhibitors	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): In the outcome measure ALI1, the number of patients after trimming belonging to the Danish Registries and treated with Empagliflozin, as well as with DPP-4 inhibitors and ≥ 3 glucose-lowering drugs, cannot be reported since the number of events in Danish Registries was 1 to 4, and the total cannot be given to avoid back-calculation of values due to the Danish small cell count policy.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence Rates of Acute Liver Injury (ALI) in Patients With no Predisposing Conditions (ALI1) in Propensity Score-trimmed Cohort for ALI1 (time frame: up to 5 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02864914.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.