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

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Empagliflozin and Dipeptidyl Peptidate-4 inhibitors
How many people: 62,197 participants
Where: 1 siteUnited States
Study dates: 8 Aug 2022to 2 May 2023
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke Clinical Research Institute
Durham, North Carolina, 27707

Other trials in United States

About this study

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

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
Being tested: Empagliflozin, Dipeptidyl Peptidate-4 inhibitors
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EmpagliflozinDrug
Empagliflozin
Dipeptidyl Peptidate-4 inhibitorsDrug
Dipeptidyl Peptidate-4 inhibitors

Study groups in NCT05465317
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Dipeptidyl Peptidate-4 inhibitors

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
40% decline in eGFR: at least 2 measurements (second measurement must be within 2 years) during follow-up of at least a 40% decline relative to baseline separated by >= 28 days.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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)
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.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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
Incident dialysis, given dialysis in the 12 months preceding index date is a disqualifying diagnosis/procedure.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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
Kidney transplant: any procedure associated with healthcare encounters, including hospitalizations and specialist outpatient and primary care encounters.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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
Composite outcome including acute hospitalization for heart failure and All-cause death: Any diagnosis of heart failure associated with hospital admission, including inpatient and emergency department (ED) to inpatient encounters. From death records provided by sites, supplemented with linkage using Datavant Software.
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 separately for the CKD and non-CKD cohorts.
Measured: 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 Acute Hospitalization for Heart Failure
Acute hospitalization for heart failure: Any diagnosis of heart failure associated with hospital admission, including inpatient and emergency department (ED) to inpatient encounters.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 All-cause Death
All-cause death, from death records provided by sites, supplemented with linkage using Datavant Software.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. a LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure
Composite outcome including MI, Stroke, All-cause death and Coronary revascularization procedure: For MI and stroke, any inpatient diagnosis associated with healthcare encounters, including inpatient and ED to inpatient For all-cause death, death records provided by sites, supplemented with linkage using Datavant Software.
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 separately for the CKD and non-CKD cohorts.
Measured: 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 the Composite Outcome Including MI, Stroke, All-cause Death (MACE)
Composite outcome including MI, Stroke, All-cause death: For MI and stroke, any inpatient diagnosis associated with healthcare encounters, including inpatient and ED to inpatient For all-cause death, death records provided by sites, supplemented with linkage using Datavant Software.
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 separately for the CKD and non-CKD cohorts.
Measured: 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 Diabetic Ketoacidosis
Any diabetic ketoacidosis diagnosis associated with healthcare encounters in the inpatient setting.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 Severe Hypoglycemia
Any severe hypoglycemia diagnosis associated with healthcare encounters in the inpatient or ED setting.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 Urinary Tract Cancer
Two or more urinary tract cancer diagnoses associated with healthcare encounters within 2 months.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 Severe Urinary Tract Infections (UTI)
Any severe Urinary Tract Infections (UTI) diagnosis associated with healthcare encounters in the inpatient or ED setting for Pyelonephritis or Urosepsis.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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 Acute Kidney Injury (AKI) That Requires Dialysis
Any Acute kidney injury diagnosis associated with inpatient healthcare encounters for AKI plus at least one inpatient encounter indicating dialysis within 28 days of the AKI encounter. Two or more dialysis encounters separated by 28 days or more was excluded from this definition.
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 separately for the CKD and non-CKD cohorts.
Measured: 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 Genital Mycotic Infection
Any genital mycotic infection diagnosis associated with healthcare encounters, including hospitalizations and outpatient encounters, or prescription for fluconazole.
Post-LASSO (least absolute shrinkage and selection operator) overlap weighting was used. A LASSO penalized regression model was created with the covariates of interest, subgroup variables, and all pairwise covariate-subgroup interactions. Outcome for this model was treatment group (DPP4i as the reference). The variables chosen by the LASSO model were refit to a logistic model in order to calculate the propensity score (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 separately for the CKD and non-CKD cohorts.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Aug 20222 May 2023

First posted19 Jul 2022
Study start8 Aug 2022
Primary completion2 May 2023
Study completion2 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 62,197 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05465317
Sponsor's protocol ID: 1245-0228
Status last verified: Apr 2024
First submitted: 15 Jul 2022
Last updated: 19 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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

Publications

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.
PubMed 39142723

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05465317
Acronym / sponsor ID: 1245-0228
Conditions: Diabetes Mellitus, Type 2
Study type: Observational
Recruitment status: Completed
Enrolment: 62,197 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 8 Aug 2022 (actual)
Primary completion: 2 May 2023 (actual)
Study completion: 2 May 2023 (actual)
First posted: 19 Jul 2022 (actual)
Results: Posted 19 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
Empagliflozin initiators	–	Drug: EmpagliflozinPatient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020.
Dipeptidyl peptidate-4 inhibitor (DPP4i) initiators	–	Drug: Dipeptidyl Peptidate-4 inhibitorsPatient 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: The analysis will include adults (≥18 years) with type 2 diabetes with or without kidney disease in the US.

Key inclusion criteria (7 listed)

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.,

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EmpagliflozinEmpagliflozin	Drug	Empagliflozin initiators
Dipeptidyl Peptidate-4 inhibitorsDipeptidyl Peptidate-4 inhibitors	Drug	Dipeptidyl peptidate-4 inhibitor (DPP4i) initiators

Primary outcome

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
Time frame: 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.
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.

15 secondary outcomes

Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Acute Hospitalization for Heart Failure
Time frame: 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 All-cause Death
Time frame: 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 the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure
Time frame: 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 the Composite Outcome Including MI, Stroke, All-cause Death (MACE)
Time frame: 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 Diabetic Ketoacidosis
Time frame: 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 Severe Hypoglycemia
Time frame: 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 Urinary Tract Cancer
Time frame: 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 Severe Urinary Tract Infections (UTI)
Time frame: 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 Acute Kidney Injury (AKI) That Requires Dialysis
Time frame: 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 Genital Mycotic Infection
Time frame: 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.

Results and safety

Results posted to the registry on 19 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Empagliflozin Initiators	20,279	20,279
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators	41,918	41,918

Primary outcome: 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

Time frame: 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.. Number. Unit: (First) events per 1000 patient years

Measure	Empagliflozin Initiators - Propensity Scored-weighted n = 20279	Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted n = 41918	Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort n = 3633	DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort n = 11126	Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort n = 16646	DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort n = 30792
Value	26.65	36.65	44.15	67.36	22.62	29.33

Empagliflozin Initiators - Propensity Scored-weighted vs Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted: Hazard Ratio (HR): 0.75 (95% CI 0.65 to 0.86), p <0.001, Regression, Cox
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort vs DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort: Hazard Ratio (HR): 0.67 (95% CI 0.52 to 0.86), p = 0.001, Regression, Cox
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort vs DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort: Hazard Ratio (HR): 0.79 (95% CI 0.67 to 0.94), p = 0.008, Regression, Cox

Population analysed: Primary study cohort: Patient with type 2 diabetes who initiated Empagliflozin or Dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. Based on existing data from 20 United States (US) health systems that have mapped their electronic health record (EHR) data to the National Patient-Centered Clinical Research Network (PCORnet) Common Data Model.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Empagliflozin Initiators	0 of 0	0 of 0	341 of 20,279
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators	0 of 0	0 of 0	1,528 of 41,918

Limitations and caveats (from the sponsor): 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).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39142723Edmonston 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.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05465317, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.