Diabetes Mellitus, Type 2
Conditions
Brief summary
The primary purpose of this research study is to determine the cardiovascular and renal effectiveness and safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with Type 2 Diabetes Mellitus (T2DM) with and without established kidney disease. The secondary purpose of this research study is to determine the cardiovascular and renal effectiveness and safety of any Sodium glucose co-transporter-2 inhibitors (SGLT2i) compared to Glucagon-like Peptide-1 Receptor Agonists (GLP1RA) in patients with T2DM.
Interventions
DRUGEmpagliflozin
Empagliflozin
DRUGDipeptidyl Peptidate-4 inhibitors
Dipeptidyl Peptidate-4 inhibitors
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥18 years old * Having a diagnosis of type 2 diabetes in 12 months before the index date (defined as the date of initiation of empagliflozin or Glucagon-like Peptide-1 Receptor Agonists (GLP1RA) or Dipeptidyl Peptidate-4 inhibitor (DPP4i), based on the cohort evaluated), based on International Classification of Diseases (ICD)-9 and -10 codes and other available data * Record of prescription for empagliflozin, any Sodium glucose co-transporter-2 inhibitors (SGLT2i), any DPP4 inhibitor, or any GLP1RA use between 1 January 2015 and 31 December 2020, and * No record of any prescription for the drugs being compared during the 12 months + 30-day grace preceding the index date period, i.e., * For the primary comparison of initiation of empagliflozin versus DPP4i, patients will not have any prescription for empagliflozin/any SGLT2i or DPP4i during the preceding 12 months + 30-day grace period. * For the comparison of initiation of SGLT2i versus GLP1RA, patients will not have any prescription for SGLT2i or GLP1RA during the preceding 12 months + 30-day grace period. * For the comparison of initiation of empagliflozin versus GLP1RA, patients will not have any prescription for empagliflozin/any SGLT2i or GLP1RA during the preceding 12 months + 30-day grace period.
Exclusion criteria
* Aged \<18 years on the first prescription date of the qualifying prescription, * Pre-existing diagnosis of type 1 diabetes mellitus (T1DM) during the 12 months before the index date, * Having a disqualifying diagnosis during the 12 months before the index date, defined as having at least one of the following: estimated glomerular filtration rate (eGFR) \<30, dialysis, polycystic kidney disease or a kidney transplant, * \<12 months of available data before the index date, and/or no complete history of drug dispensations/other records of drug use during this period, defined as not having at least 1 ambulatory visit and at least 1 medication prescription during the preceding 12 months, and * Missing or ambiguous data on serum creatinine in the 12 months prior to the index date or sex
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of End-stage Kidney Disease (ESKD) | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Dialysis | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Kidney Transplant | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Acute Hospitalization for Heart Failure | 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. | 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. |
| Incidence Rate of All-cause Death | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 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. | 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. |
| Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Diabetic Ketoacidosis | 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. | 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. |
| Incidence Rate of Severe Hypoglycemia | 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. | 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. |
| Incidence Rate of Urinary Tract Cancer | 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. | 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. |
| Incidence Rate of Severe Urinary Tract Infections (UTI) | 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. | 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. |
| Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | Starting the day after the index date (date of initiation of empagliflozin or DPP4i) and continuing until the first occurrence of the outcome of interest, or end of study date (date of death, date of study end, 2 years after index date). Up to 2 years. | 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. |
| Incidence Rate of Genital Mycotic Infection | 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. | 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. |
| Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 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. | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 20,279 |
| 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. | 41,918 |
| Total | 62,197 |
Baseline characteristics
| Characteristic | Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators | Total | Empagliflozin Initiators |
|---|---|---|---|
| Age, Continuous | 63.0 years | 62.0 years | 60.0 years |
| Race/Ethnicity, Customized Black | 9641 Participants | 13839 Participants | 4198 Participants |
| Race/Ethnicity, Customized Other | 2767 Participants | 3842 Participants | 1075 Participants |
| Race/Ethnicity, Customized White | 29510 Participants | 44516 Participants | 15006 Participants |
| Sex: Female, Male Female | 22007 Participants | 31558 Participants | 9551 Participants |
| Sex: Female, Male Male | 19911 Participants | 30639 Participants | 10728 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 341 / 20,279 | 1,528 / 41,918 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - 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 | 26.65 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - 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 |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | 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 | 44.15 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | 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 | 67.36 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | 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 | 22.62 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | 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 | 29.33 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: <0.00195% CI: [0.65, 0.86]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.00195% CI: [0.52, 0.86]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.00895% CI: [0.67, 0.94]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Acute Hospitalization for Heart Failure | 12.74 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Acute Hospitalization for Heart Failure | 14.40 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Acute Hospitalization for Heart Failure | 29.47 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Acute Hospitalization for Heart Failure | 33.08 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Acute Hospitalization for Heart Failure | 8.92 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Acute Hospitalization for Heart Failure | 9.95 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.3295% CI: [0.72, 1.11]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.595% CI: [0.65, 1.24]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.595% CI: [0.68, 1.2]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 1.23 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 1.45 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 2.53 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 4.02 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 0.93 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Acute Kidney Injury (AKI) That Requires Dialysis | 0.83 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.6295% CI: [0.43, 1.66]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.3195% CI: [0.21, 1.64]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.7695% CI: [0.46, 2.92]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of All-cause Death | 13.47 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of All-cause Death | 18.60 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of All-cause Death | 23.75 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of All-cause Death | 35.56 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of All-cause Death | 11.09 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of All-cause Death | 14.49 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.00595% CI: [0.62, 0.92]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0395% CI: [0.49, 0.96]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.07495% CI: [0.63, 1.02]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | 24.65 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - 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 |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | 50.05 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | 61.34 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | 18.86 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Composite Outcome Including Acute Hospitalization for Heart Failure and All-cause Death | 22.83 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0295% CI: [0.72, 0.97]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.1295% CI: [0.65, 1.05]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.195% CI: [0.7, 1.03]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Diabetic Ketoacidosis | 4.06 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Diabetic Ketoacidosis | 2.86 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Diabetic Ketoacidosis | 3.59 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Diabetic Ketoacidosis | 3.46 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Diabetic Ketoacidosis | 4.17 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Diabetic Ketoacidosis | 2.71 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.1595% CI: [0.89, 2.1]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.9395% CI: [0.4, 2.72]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.11395% CI: [0.91, 2.38]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Dialysis | 3.47 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Dialysis | 4.76 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Dialysis | 7.86 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Dialysis | 12.03 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Dialysis | 2.46 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Dialysis | 3.01 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.1295% CI: [0.35, 1.12]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.1195% CI: [0.49, 1.08]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.5295% CI: [0.5, 1.42]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of End-stage Kidney Disease (ESKD) | 3.34 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of End-stage Kidney Disease (ESKD) | 4.90 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of End-stage Kidney Disease (ESKD) | 8.18 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of End-stage Kidney Disease (ESKD) | 12.96 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of End-stage Kidney Disease (ESKD) | 2.23 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of End-stage Kidney Disease (ESKD) | 2.97 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0595% CI: [0.46, 1]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0995% CI: [0.35, 1.09]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.395% CI: [0.43, 1.29]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Genital Mycotic Infection | 115.96 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Genital Mycotic Infection | 65.32 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Genital Mycotic Infection | 99.20 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Genital Mycotic Infection | 52.23 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Genital Mycotic Infection | 119.94 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Genital Mycotic Infection | 68.52 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: <0.00195% CI: [1.58, 1.88]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: <0.00195% CI: [1.48, 2.3]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: <0.00195% CI: [1.54, 1.87]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Kidney Transplant | 0.02 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Kidney Transplant | 0.06 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Kidney Transplant | 0.10 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Kidney Transplant | 0.10 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Kidney Transplant | 0.00 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Kidney Transplant | 0.05 (First) events per 1000 patient years |
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Severe Hypoglycemia | 9.43 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Severe Hypoglycemia | 10.69 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Severe Hypoglycemia | 14.90 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Severe Hypoglycemia | 18.89 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Severe Hypoglycemia | 8.17 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Severe Hypoglycemia | 8.72 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.4395% CI: [0.71, 1.16]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.3295% CI: [0.51, 1.24]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.8195% CI: [0.71, 1.3]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Severe Urinary Tract Infections (UTI) | 0.69 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Severe Urinary Tract Infections (UTI) | 1.01 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Severe Urinary Tract Infections (UTI) | 0.90 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Severe Urinary Tract Infections (UTI) | 2.00 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Severe Urinary Tract Infections (UTI) | 0.64 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Severe Urinary Tract Infections (UTI) | 0.77 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.3995% CI: [0.29, 1.62]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.3495% CI: [0.09, 2.27]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.7295% CI: [0.29, 2.33]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 12.10 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 16.55 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 16.46 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 27.39 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 11.10 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the 40% Decline in Estimated Glomerular Filtration Rate (eGFR) | 13.95 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.00595% CI: [0.6, 0.91]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0295% CI: [0.41, 0.91]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0895% CI: [0.63, 1.03]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 97.31 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - 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 |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 169.32 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 164.13 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 81.63 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death and Coronary Revascularization Procedure | 80.89 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.4695% CI: [0.95, 1.12]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.6395% CI: [0.9, 1.2]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.5295% CI: [0.94, 1.14]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 23.93 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 30.27 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 40.65 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 55.67 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 20.07 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of the Composite Outcome Including MI, Stroke, All-cause Death (MACE) | 24.18 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.00795% CI: [0.7, 0.94]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.0395% CI: [0.57, 0.97]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.195% CI: [0.71, 1.03]Regression, Cox
Secondary
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.
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empagliflozin Initiators - Propensity Scored-weighted | Incidence Rate of Urinary Tract Cancer | 4.65 (First) events per 1000 patient years |
| Dipeptidyl Peptidate-4 Inhibitor (DPP4i) Initiators - Propensity Scored-weighted | Incidence Rate of Urinary Tract Cancer | 5.14 (First) events per 1000 patient years |
| Empagliflozin Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Urinary Tract Cancer | 8.62 (First) events per 1000 patient years |
| DPP4i Initiators - Chronic Kidney Disease (CKD) Cohort | Incidence Rate of Urinary Tract Cancer | 9.35 (First) events per 1000 patient years |
| Empagliflozin Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Urinary Tract Cancer | 3.74 (First) events per 1000 patient years |
| DPP4i Initiators - Non-Chronic Kidney Disease (Non-CKD) Cohort | Incidence Rate of Urinary Tract Cancer | 4.13 (First) events per 1000 patient years |
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.6995% CI: [0.65, 1.33]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.8295% CI: [0.51, 1.7]Regression, Cox
Comparison: Outcomes were assessed using Cox proportional hazards (PH) models in a 2-arm comparison. The analysis included all patients with a valid overlap weight and was performed using the reweighted population. The main analysis assessed outcomes while patients remain on initial treatment.p-value: 0.7695% CI: [0.6, 1.45]Regression, Cox