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

Study Overview
=================
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.

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

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Empagliflozin
* Drug: DPP-4 inhibitors


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Empagliflozin<br>Patients initiating Empagliflozin treatment within the study period | Drug: Empagliflozin<br>* drug<br>|
| DPP-4 inhibitors<br>Patients initiating DPP-4 inhibitor treatment within the study period | Drug: DPP-4 inhibitors<br>* drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |