Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease

Study Overview
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Brief Summary
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The primary purpose of this research study is to determine the cardiovascular and renal effectiveness and safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with Type 2 Diabetes Mellitus (T2DM) with and without established kidney disease. The secondary purpose of this research study is to determine the cardiovascular and renal effectiveness and safety of any Sodium glucose co-transporter-2 inhibitors (SGLT2i) compared to Glucagon-like Peptide-1 Receptor Agonists (GLP1RA) in patients with T2DM.

Official Title
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Comparative Cardiovascular and Renal Effectiveness and Safety of Empagliflozin and Other SGLT2i in Patients With Type 2 Diabetes (T2D) With and Without Baseline Kidney Disease in the United States

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Dipeptidyl Peptidate-4 inhibitors
* Drug: Sodium glucose co-transporter-2 inhibitors
* Drug: Glucagon-like Peptide-1 Receptor Agonists


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients ≥18 years old Having a diagnosis of type 2 diabetes in 12 months before the index date (defined as the date of initiation of empagliflozin or Glucagon-like Peptide-1 Receptor Agonists (GLP1RA) or Dipeptidyl Peptidate-4 inhibitor (DPP4i), based on the cohort evaluated), based on International Classification of Diseases (ICD)-9 and -10 codes and other available data Record of prescription for empagliflozin, any Sodium glucose co-transporter-2 inhibitors (SGLT2i), any DPP4 inhibitor, or any GLP1RA use between 1 January 2015 and 31 December 2020, and No record of any prescription for the drugs being compared during the 12 months + 30-day grace preceding the index date period, i.e., For the primary comparison of initiation of empagliflozin versus DPP4i, patients will not have any prescription for empagliflozin/any SGLT2i or DPP4i during the preceding 12 months + 30-day grace period. For the comparison of initiation of SGLT2i versus GLP1RA, patients will not have any prescription for SGLT2i or GLP1RA during the preceding 12 months + 30-day grace period. For the comparison of initiation of empagliflozin versus GLP1RA, patients will not have any prescription for empagliflozin/any SGLT2i or GLP1RA during the preceding 12 months + 30-day grace period. Exclusion criteria: Aged <18 years on the first prescription date of the qualifying prescription, Pre-existing diagnosis of type 1 diabetes mellitus (T1DM) during the 12 months before the index date, Having a disqualifying diagnosis during the 12 months before the index date, defined as having at least one of the following: estimated glomerular filtration rate (eGFR) <30, dialysis, polycystic kidney disease or a kidney transplant, <12 months of available data before the index date, and/or no complete history of drug dispensations/other records of drug use during this period, defined as not having at least 1 ambulatory visit and at least 1 medication prescription during the preceding 12 months, and Missing or ambiguous data on serum creatinine in the 12 months prior to the index date or sex

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Type 2 Diabetes Mellitus (T2DM)<br> | Drug: Empagliflozin<br>* Empagliflozin<br>Drug: Dipeptidyl Peptidate-4 inhibitors<br>* Dipeptidyl Peptidate-4 inhibitors<br>Drug: Sodium glucose co-transporter-2 inhibitors<br>* Sodium glucose co-transporter-2 inhibitors<br>Drug: Glucagon-like Peptide-1 Receptor Agonists<br>* Glucagon-like Peptide-1 Receptor Agonists<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome including: 40% decline in estimated glomerular filtration rate (eGFR), incident end-stage kidney disease (ESKD), all-cause mortality | 40% decline in eGFR: at least 2 measurements during follow-up of at least a 40% decline relative to baseline separated by ≥ 28 days ESKD definition: at least 1 kidney transplant or ESKD diagnosis/procedure or at least 2 dialysis diagnoses/procedures separated by ≥ 28 days or eGFR<15 on 2 measurements separated by ≥ 28 days | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 40% decline in eGFR |  | up to 2 years | 
| Incident end-stage kidney disease (ESKD) |  | up to 2 years | 
| Incident dialysis |  | up to 2 years | 
| Kidney transplant |  | up to 2 years | 
| Composite outcome including: hospitalization for heart failure and all-cause mortality |  | up to 2 years | 
| Incidence of hospitalization for heart failure |  | up to 2 years | 
| All-cause mortality |  | up to 2 years | 
| Composite outcome including: myocardial infarction (MI), stroke, all-cause mortality, coronary revascularization procedure |  | up to 2 years | 
| Composite outcome including: MI, stroke, all-cause mortality |  | up to 2 years | 
| Diabetic ketoacidosis |  | up to 2 years | 
| Severe hypoglycemia |  | up to 2 years | 
| Urinary tract cancer |  | up to 2 years | 
| Severe Urinary Tract Infections (UTI) |  | up to 2 years | 
| Acute kidney injury that requires dialysis |  | up to 2 years | 
| Genital Mycotic infection |  | up to 2 years |