Trial Outcomes & Findings for Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease (NCT NCT05465317)

NCT ID: NCT05465317

Last Updated: 2024-09-19

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

62197 participants

Primary outcome timeframe

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 posted on

2024-09-19

Participant Flow

This was a non-interventional, retrospective cohort study (NIS) using existing data from 20 US health systems, the study period was from 1 Jan 2014 through 31 December 2021, to determine the cardiovascular and renal effectiveness and safety up to 24 months after initiation of empagliflozin compared to dipeptidyl peptidate-4 inhibitor (DPP4i) in patients with type 2 diabetes.

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study.

Participant milestones

Participant milestones
Measure
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.
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.
Overall Study
STARTED
20279
41918
Overall Study
COMPLETED
20279
41918
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Empagliflozin Initiators
n=20279 Participants
Patient 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
n=41918 Participants
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.
Total
n=62197 Participants
Total of all reporting groups
Age, Continuous
60.0 years
n=5 Participants
63.0 years
n=7 Participants
62.0 years
n=5 Participants
Sex: Female, Male
Female
9551 Participants
n=5 Participants
22007 Participants
n=7 Participants
31558 Participants
n=5 Participants
Sex: Female, Male
Male
10728 Participants
n=5 Participants
19911 Participants
n=7 Participants
30639 Participants
n=5 Participants
Race/Ethnicity, Customized
White
15006 Participants
n=5 Participants
29510 Participants
n=7 Participants
44516 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
4198 Participants
n=5 Participants
9641 Participants
n=7 Participants
13839 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
1075 Participants
n=5 Participants
2767 Participants
n=7 Participants
3842 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
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
36.65 (First) events per 1000 patient years
44.15 (First) events per 1000 patient years
67.36 (First) events per 1000 patient years
22.62 (First) events per 1000 patient years
29.33 (First) events per 1000 patient years
26.65 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR)
16.55 (First) events per 1000 patient years
16.46 (First) events per 1000 patient years
27.39 (First) events per 1000 patient years
11.10 (First) events per 1000 patient years
13.95 (First) events per 1000 patient years
12.10 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of End-stage Kidney Disease (ESKD)
4.90 (First) events per 1000 patient years
8.18 (First) events per 1000 patient years
12.96 (First) events per 1000 patient years
2.23 (First) events per 1000 patient years
2.97 (First) events per 1000 patient years
3.34 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Dialysis
4.76 (First) events per 1000 patient years
7.86 (First) events per 1000 patient years
12.03 (First) events per 1000 patient years
2.46 (First) events per 1000 patient years
3.01 (First) events per 1000 patient years
3.47 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Kidney Transplant
0.06 (First) events per 1000 patient years
0.10 (First) events per 1000 patient years
0.10 (First) events per 1000 patient years
0.00 (First) events per 1000 patient years
0.05 (First) events per 1000 patient years
0.02 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death
30.24 (First) events per 1000 patient years
50.05 (First) events per 1000 patient years
61.34 (First) events per 1000 patient years
18.86 (First) events per 1000 patient years
22.83 (First) events per 1000 patient years
24.65 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Acute Hospitalization for Heart Failure
14.40 (First) events per 1000 patient years
29.47 (First) events per 1000 patient years
33.08 (First) events per 1000 patient years
8.92 (First) events per 1000 patient years
9.95 (First) events per 1000 patient years
12.74 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of All-cause Death
18.60 (First) events per 1000 patient years
23.75 (First) events per 1000 patient years
35.56 (First) events per 1000 patient years
11.09 (First) events per 1000 patient years
14.49 (First) events per 1000 patient years
13.47 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure
96.36 (First) events per 1000 patient years
169.32 (First) events per 1000 patient years
164.13 (First) events per 1000 patient years
81.63 (First) events per 1000 patient years
80.89 (First) events per 1000 patient years
97.31 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE)
30.27 (First) events per 1000 patient years
40.65 (First) events per 1000 patient years
55.67 (First) events per 1000 patient years
20.07 (First) events per 1000 patient years
24.18 (First) events per 1000 patient years
23.93 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Diabetic Ketoacidosis
2.86 (First) events per 1000 patient years
3.59 (First) events per 1000 patient years
3.46 (First) events per 1000 patient years
4.17 (First) events per 1000 patient years
2.71 (First) events per 1000 patient years
4.06 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Severe Hypoglycemia
10.69 (First) events per 1000 patient years
14.90 (First) events per 1000 patient years
18.89 (First) events per 1000 patient years
8.17 (First) events per 1000 patient years
8.72 (First) events per 1000 patient years
9.43 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Urinary Tract Cancer
5.14 (First) events per 1000 patient years
8.62 (First) events per 1000 patient years
9.35 (First) events per 1000 patient years
3.74 (First) events per 1000 patient years
4.13 (First) events per 1000 patient years
4.65 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Severe Urinary Tract Infections (UTI)
1.01 (First) events per 1000 patient years
0.90 (First) events per 1000 patient years
2.00 (First) events per 1000 patient years
0.64 (First) events per 1000 patient years
0.77 (First) events per 1000 patient years
0.69 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis
1.45 (First) events per 1000 patient years
2.53 (First) events per 1000 patient years
4.02 (First) events per 1000 patient years
0.93 (First) events per 1000 patient years
0.83 (First) events per 1000 patient years
1.23 (First) events per 1000 patient years

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted
n=41918 Participants
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. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort
n=3633 Participants
Patient with type 2 diabetes, with established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort
n=11126 Participants
Patient with type 2 diabetes with established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=16646 Participants
Patient with type 2 diabetes, without established Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort
n=30792 Participants
Patient with type 2 diabetes without established Chronic Kidney Disease (CKD), who initiated dipeptidyl peptidate-4 inhibitor (DPP4i) between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Empagliflozin Initiators - Propensity Scored-weighted
n=20279 Participants
Patient with type 2 diabetes, with or without Chronic Kidney Disease (CKD), who initiated Empagliflozin between January 1, 2016 and December 31, 2020. The cohort was propensity scored-weighted.
Incidence Rate of Genital Mycotic Infection
65.32 (First) events per 1000 patient years
99.20 (First) events per 1000 patient years
52.23 (First) events per 1000 patient years
119.94 (First) events per 1000 patient years
68.52 (First) events per 1000 patient years
115.96 (First) events per 1000 patient years

Adverse Events

Empagliflozin Initiators

Serious events: 0 serious events
Other events: 0 other events
Deaths: 341 deaths

Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators

Serious events: 0 serious events
Other events: 0 other events
Deaths: 1528 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim , Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
  • Publication restrictions are in place

Restriction type: OTHER