Empagliflozin

Time to first occurrence of kidney disease progression (KDP) or cardiovascular death is reported as incidence rate of first occurrence of KDP or adjudicated cardiovascular death. Incidence rate= (Number of patients who experienced the event of first occurrence of KDP or cardiovascular death)\*100/(patient years at risk (pt-yrs at risk). pt-yrs at risk= sum of time at risk \[days\] over all patients in a treatment group / 365.25. Kidney disease progression was defined as: * end stage kidney disease (defined as the initiation of maintenance dialysis or receipt of a kidney transplant) OR * a sustained decline in estimated glomerular filtration rate (eGFR) to \<10 mL/min/1.73m\^2 OR * renal death OR * a sustained decline of ≥40% in eGFR from randomisation.

Time to first occurrence of kidney disease progression (KDP) or cardiovascular death is reported as incidence of progression of kidney disease or death from cardiovascular causes in the interventional part of the trial and in the post-trial follow-up (non-interventional part). Incidence rate= (Number of patients who experienced the event of first occurrence of KDP or cardiovascular death)\*100/(patient years at risk (pt-yrs at risk). pt-yrs at risk= sum of time at risk \[days\] over all patients in a treatment group / 365.25. Kidney disease progression was defined as: * a sustained decline in eGFR to less than 10 mL/min/1.73m\^2 OR * renal death OR * sustained decline of more than 40% in eGFR from randomization.

Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. If repeated 6MWT measurements were available for the same day, the longest distance was used for analysis. Change from baseline was defined as the distance walked in 6 minutes at week 12 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. If a participant was present at the visit at week 12 but did not perform the 6MWT, the participant was evaluated as having walked a distance of 0 meter. If no value was available for week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above.

The composite of time to first heart failure hospitalization or all-cause mortality is reported as the incidence rate of the first occurrence of hospitalization for heart failure (HHF) or death, whichever is earliest. The incidence rate was calculated as: the number of patients with an event for hospitalization for heart failure or death by treatment group during time at risk divided by the total time patients were at risk in that treatment group multiplied by 100 (per 100 Pt-years, Pt as abbreviation of patient).

Clinical benefit, a composite of death, number of HFEs, time to first HFE and change from baseline (CfB) in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) after 90 days of treatment. All patients randomised to empagliflozin are compared to all patients randomised to placebo within strata. For any two patients, a patient will win, i.e. achieve a better clinical outcome, as determined by assessing the following criteria sequentially, stopping when an advantage for either patient is shown: 1. Death: death is worse than no death; earlier death is worse; tied if not possible to determine. 2. Number of HFEs: more HFEs is worse; tied, if same number of HFEs. 3. Time to first HFE: earlier HFE is worse; tied, if not possible to determine. 4. KCCQ-TSS CfB at Day 90: more positive CfB is better; the threshold for the difference is \>= 5 for a win; tied, if difference \< 5. The KCCQ-TSS ranges from 0 to 100, where a higher score reflects a better outcome. pct. = percentage

Failure with preserved Ejection Fraction (HFpEF). The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.

This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point. Time frame description: The time -1:00 hour (h) was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-tz (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point).

This outcome measure presents area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-72 (area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours).

This outcome measure presents maximum measured concentration of Empagliflozin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Empagliflozin analyte in plasma).

This outcome measure presents maximum measured concentration of Linagliptin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Linagliptin analyte in plasma).

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) for empagliflozin. Plasma concentrations and/or parameters of a subject were to be considered as non-evaluable,if for example: * The subject experienced emesis that occurred at or before 2 times median tmax of the respective treatment (median tmax was to be determined excluding the subjects experiencing emesis) * A predose concentration was \>5% Cmax value of that subject * Missing samples/concentration data at important phases of pharmacokinetic (PK) disposition curve. Pharmacokinetic parameter set (PKS): This subject set included all subjects in the treated set (TS) who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was to be included in the PKS even if he/she contributed only one PK parameter value for one period to the statistical assessment.

AUC0-tz for metformin.

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for Linagliptin

Maximum measured concentration of the empagliflozin in plasma (Cmax)

Cmax for metformin in plasma.

Cmax for linagliptin in plasma.

Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)

Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)

Maximum measured concentration of the empagliflozin in plasma

Maximum measured concentration of the metformin in plasma

Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity

Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity

Maximum measured concentration of the empagliflozin in plasma

Maximum measured concentration of the metformin in plasma