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

NCT05465317 | Completed Results FDA Drug

• 1 other identifier: 1245-0228
• Study Type: observational
• Target: 62,197
• Locations: 1 country
• Sites: 1

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) in patients with T2DM.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Incidence Rate of the Composite Outcome Including 40% Decline in Estimated Glomerular Filtration Rate (eGFR), Incident End-stage Renal Disease (ESRD) and All-cause Death

  40% decline in eGFR: at least 2 measurements during follow-up of at least a 40% decline relative to baseline separated by \>= 28 days. the second eGFR measurement is required to be within 2 years from index, at which time, all patients were censored. ESKD: 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. Post-LASSO overlap weighting was used. A LASSO penalized regression model was created with covariates of interest, subgroup variables, and all pairwise interactions. Variables chosen by the LASSO model were refit to a logistic model in order to calculate the PS estimates. The overlap weights were then created such that the weights were equal to the PS for participants prescribed the reference treatment (DPP4i) and 1-PS for participants prescribed empagliflozin. Results are presented for the overall cohort and for the CKD and non-CKD cohorts.

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

Secondary Outcomes (15)

• Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR)

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

• Incidence Rate of End-stage Kidney Disease (ESKD)

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

• Incidence Rate of Dialysis

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

• Incidence Rate of Kidney Transplant

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

• Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death

  Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years.

Study Arms (2)

Empagliflozin initiators

Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020.

Drug: Empagliflozin

Dipeptidyl peptidate-4 inhibitor (DPP4i) initiators

Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020.

Drug: Dipeptidyl Peptidate-4 inhibitors

Interventions

Empagliflozin DRUG

Empagliflozin

Empagliflozin initiators

Dipeptidyl Peptidate-4 inhibitors DRUG

Dipeptidyl Peptidate-4 inhibitors

Dipeptidyl peptidate-4 inhibitor (DPP4i) initiators

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Duke Clinical Research Institute

Durham, North Carolina, 27707, United States

Location

Related Publications (1)

• Edmonston D, Mulder H, Lydon E, Chiswell K, Lampron Z, Shay C, Marsolo K, Shah RC, Jones WS, Gordon H, Hwang W, Ayoub I, Ford D, Chamberlain A, Rao A, Fonseca V, Chang A, Ahmad F, Hung A, Hunt K, Butler J, Bosworth HB, Pagidipati N. Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes. J Am Coll Cardiol. 2024 Aug 20;84(8):696-708. doi: 10.1016/j.jacc.2024.06.016.

  PMID: 39142723 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

Limitations inherent to all electronic health record (EHR) based studies, including potential for missing data (i.e., data that was generated through a different health system) or inaccurate data based on billing codes. This limitation could have resulted in HCRU not captured in the current study which could have attenuated the observed results (e.g., medications, hospitalizations, etc).

Results Point of Contact

• Title: Boehringer Ingelheim , Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 19, 2022
• Study Start: August 8, 2022
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)