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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Empagliflozin; Drug: Dipeptidyl Peptidate-4 inhibitors; Drug: Sodium glucose co-transporter-2 inhibitors; Drug: Glucagon-like Peptide-1 Receptor Agonists

• Study Type: Observational
• Enrollment (Actual): 30400

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Duke Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The analysis will include adults (≥18 years) with type 2 diabetes with or without kidney disease in the US.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

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	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
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
Composite outcome including: MI, stroke, all-cause mortality	up to 2 years

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2022
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Empagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Glucagon-Like Peptide 1
• Other Study ID Numbers: 1245-0228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No