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

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT02864914

Collaborator

Eli Lilly and Company (Industry)

99,000

Enrollment

Location

76.5

Actual Duration (Months)

1294.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Empagliflozin Drug: DPP-4 inhibitors

Study Design

Study Type:

Observational

Actual Enrollment :

99000 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

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

Actual Study Start Date :

Mar 15, 2016

Actual Primary Completion Date :

Jul 29, 2022

Actual Study Completion Date :

Jul 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Empagliflozin Patients initiating Empagliflozin treatment within the study period	Drug: Empagliflozin drug
DPP-4 inhibitors Patients initiating DPP-4 inhibitor treatment within the study period	Drug: DPP-4 inhibitors drug

Arm

Intervention/Treatment

Empagliflozin

Patients initiating Empagliflozin treatment within the study period

Drug: Empagliflozin

drug

DPP-4 inhibitors

Patients initiating DPP-4 inhibitor treatment within the study period

Drug: DPP-4 inhibitors

drug

Outcome Measures

Primary Outcome Measures

Acute liver injury (ALI) in patients with no predisposing conditions [up to 5 years]
Acute kidney injury (AKI) [up to 5 years]
Severe complications of urinary tract infections (UTIs) [up to 5 years]
Genital infections [up to 5 years]
Incidence of diabetic ketoacidosis (DKA) [up to 5 years]

Secondary Outcome Measures

Acute liver injury in patients with or without predisposing conditions [up to 5 years]
Chronic kidney disease (CKD) [up to 5 years]
Incidence of severe genital infections [up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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