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

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05465317

Collaborator

(none)

30,400

Enrollment

Location

Anticipated Duration (Days)

132185.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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), and empagliflozin compared to GLP1RA in patients with T2DM.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Empagliflozin Drug: Dipeptidyl Peptidate-4 inhibitors Drug: Sodium glucose co-transporter-2 inhibitors Drug: Glucagon-like Peptide-1 Receptor Agonists

Study Design

Study Type:

Observational

Anticipated Enrollment :

30400 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Anticipated Study Start Date :

Aug 13, 2022

Anticipated Primary Completion Date :

Aug 20, 2022

Anticipated Study Completion Date :

Aug 20, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Patients with Type 2 Diabetes Mellitus (T2DM)

Drug: Empagliflozin

Empagliflozin

Drug: Dipeptidyl Peptidate-4 inhibitors

Dipeptidyl Peptidate-4 inhibitors

Drug: Sodium glucose co-transporter-2 inhibitors

Sodium glucose co-transporter-2 inhibitors

Drug: Glucagon-like Peptide-1 Receptor Agonists

Glucagon-like Peptide-1 Receptor Agonists

Outcome Measures

Primary Outcome Measures

Composite outcome including: 40% decline in estimated glomerular filtration rate (eGFR), incident end-stage kidney disease (ESKD), all-cause mortality [up to 2 years]
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

Secondary Outcome Measures

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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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