Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial will evaluate use of BI 10773/linagliptin once daily (qd) fixed dose combination (FDC) in treatment naïve and metformin treated patients with type 2 diabetes mellitus to support approval by regulatory authorities.
Interventions
DRUGhigh dose FDC
once daily
once daily
DRUGhigh dose FDC placebo
once daily
DRUGlow dose FDC placebo
once daily
DRUGhigh dose BI 10773 placebo
once daily
DRUGlow dose FDC
once daily
low dose once daily
DRUGlinagliptin
once daily
once daily
DRUGBI 10773 low dose placebo
once daily
DRUGlow dose BI 10773 placebo
once daily
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of type 2 diabetes mellitus prior to informed consent 2. Male and female patients on diet and exercise regimen who are drug-naïve (defined as absence of any oral antidiabetic therapy, glucagon like peptide-1 analog or insulin for 12 weeks prior to randomization) or pre-treated with metformin (=1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. 3. Glycosylated hemoglobin (HbA1c) = 7.0% and = 10.5% (= 53.0 mmol/mol and = 91.3 mmol/mol) at Visit 1 (screening)
Exclusion criteria
1. Uncontrolled hyperglycemia with a glucose level \>240 mg/dl (\>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day). 2. Any other antidiabetic drug within 12 weeks prior to randomization (except metformin background therapy as defined via inclusion criterion 2) 3. Acute coronary syndrome (non-ST elevation myocardial infarction, ST elevation myocardial infarction and unstable angina pectoris), stroke or (transient ischemic attack) TIA within 3 months prior to informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | Baseline and 24 weeks | Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | Baseline and 24 weeks | Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight for Metformin Background Patients | Baseline and 24 Weeks | Change from baseline in body weight for Metformin Background patients. |
| Change From Baseline in Body Weight for Treatment Naive Patients | Baseline and 24 Weeks | Change from baseline in body weight for Treatment Naive patients. |
| Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | Baseline and 24 Weeks | Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients. |
| Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 24 Weeks | Occurrence of the treat-to-target efficacy response for Treatment Naive patients measured as HbA1c \< 7.0% after 24 weeks of treatment for patients with HbA1c \>=7.0% at baseline. |
| Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 24 Weeks | Occurrence of the treat-to-target efficacy response for Metformin Background patients measured as HbA1c \< 7.0% after 24 weeks of treatment for patients with HbA1c \>=7.0% at baseline. |
| Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | Baseline and 24 Weeks | Change from baseline in fasting plasma glucose at week 24 for Treatment Naive patients. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Colombia, Denmark, Estonia, Hungary, Italy, Lebanon, Malaysia, Mexico, Peru, Philippines, Poland, Romania, Russia, Spain, Sweden, Taiwan, United States
Participant flow
Pre-assignment details
Of the 1405 patients enrolled and randomized the data for 42 randomized patients were excluded from all analyses due to serious non-compliance. Therefore, 1363 patients were included in the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral | 134 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral | 135 |
| Metformin Background: Empagliflozin 25 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral | 140 |
| Metformin Background: Empagliflozin 10 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral | 137 |
| Metformin Background: Linagliptin 5 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral | 128 |
| Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral | 134 |
| Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral | 135 |
| Treatment Naive: Empagliflozin 25 mg Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral | 133 |
| Treatment Naive: Empagliflozin 10 mg Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral | 132 |
| Treatment Naive: Linagliptin 5 mg Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral | 133 |
| Total | 1,341 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 24 | Consent withdrawn | 5 | 1 | 3 | 4 | 5 | 6 | 5 | 4 | 3 | 6 |
| Week 24 | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Week 24 | Lost to Follow-up | 1 | 1 | 2 | 4 | 2 | 0 | 1 | 3 | 3 | 4 |
| Week 52 | Consent withdrawn | 9 | 4 | 6 | 12 | 7 | 12 | 10 | 12 | 13 | 9 |
| Week 52 | Death | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 3 | 1 | 0 |
| Week 52 | Lost to Follow-up | 3 | 5 | 7 | 5 | 8 | 5 | 5 | 8 | 7 | 8 |
Baseline characteristics
| Characteristic | Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Metformin Background: Empagliflozin 25 mg | Metformin Background: Empagliflozin 10 mg | Metformin Background: Linagliptin 5 mg | Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg | Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg | Treatment Naive: Empagliflozin 25 mg | Treatment Naive: Empagliflozin 10 mg | Treatment Naive: Linagliptin 5 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 10.2 | 56.2 years STANDARD_DEVIATION 10.3 | 55.5 years STANDARD_DEVIATION 10 | 56.1 years STANDARD_DEVIATION 10.5 | 56.2 years STANDARD_DEVIATION 10 | 54.2 years STANDARD_DEVIATION 10 | 55.2 years STANDARD_DEVIATION 9.8 | 56.0 years STANDARD_DEVIATION 9.3 | 53.9 years STANDARD_DEVIATION 10.5 | 53.8 years STANDARD_DEVIATION 11.5 | 55.4 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 62 Participants | 52 Participants | 75 Participants | 59 Participants | 64 Participants | 64 Participants | 62 Participants | 56 Participants | 68 Participants | 58 Participants | 620 Participants |
| Sex: Female, Male Male | 72 Participants | 83 Participants | 65 Participants | 78 Participants | 64 Participants | 70 Participants | 73 Participants | 77 Participants | 64 Participants | 75 Participants | 721 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 80 / 273 | 86 / 272 | 70 / 276 | 83 / 275 | 94 / 267 |
| serious Total, serious adverse events | 12 / 273 | 16 / 272 | 19 / 276 | 16 / 275 | 10 / 267 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients
Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.
Time frame: Baseline and 24 weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | -1.19 % change from baseline | Standard Error 0.06 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | -1.08 % change from baseline | Standard Error 0.06 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | -0.62 % change from baseline | Standard Error 0.06 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | -0.66 % change from baseline | Standard Error 0.06 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | -0.70 % change from baseline | Standard Error 0.06 |
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p\<0.0001), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.75, -0.41]ANCOVA
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p\<0.0001), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.67, -0.32]ANCOVA
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p\<0.0001), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.59, -0.25]ANCOVA
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p\<0.0001), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.56, -0.21]ANCOVA
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients
Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.
Time frame: Baseline and 24 weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised to and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | -1.08 % change from baseline | Standard Error 0.07 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | -1.24 % change from baseline | Standard Error 0.07 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | -0.95 % change from baseline | Standard Error 0.07 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | -0.83 % change from baseline | Standard Error 0.07 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | -0.67 % change from baseline | Standard Error 0.07 |
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p\<0.0001) as fixed effect(s).p-value: 0.178595% CI: [-0.33, 0.06]ANCOVA
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.61, -0.21]ANCOVA
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.61, -0.22]Cochran-Mantel-Haenszel
Comparison: Model for Week 24 includes baseline HbA1c (p\<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.8627), geographical region (p=0.0008), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-0.76, -0.37]ANCOVA
Secondary
Change From Baseline in Body Weight for Metformin Background Patients
Change from baseline in body weight for Metformin Background patients.
Time frame: Baseline and 24 Weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Body Weight for Metformin Background Patients | -2.99 kg change from baseline | Standard Error 0.31 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Body Weight for Metformin Background Patients | -2.60 kg change from baseline | Standard Error 0.3 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Body Weight for Metformin Background Patients | -3.18 kg change from baseline | Standard Error 0.3 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Body Weight for Metformin Background Patients | -2.53 kg change from baseline | Standard Error 0.3 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Body Weight for Metformin Background Patients | -0.69 kg change from baseline | Standard Error 0.31 |
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p\<0.0001) as fixed effect(s).p-value: 0.875795% CI: [-0.91, 0.77]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p\<0.0001) as fixed effect(s).p-value: 0.660495% CI: [-0.65, 1.03]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-3.15, -1.44]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.1610) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0162), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-2.77, -1.05]ANCOVA
Secondary
Change From Baseline in Body Weight for Treatment Naive Patients
Change from baseline in body weight for Treatment Naive patients.
Time frame: Baseline and 24 Weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Body Weight for Treatment Naive Patients | -2.00 kg change from baseline | Standard Error 0.36 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Body Weight for Treatment Naive Patients | -2.74 kg change from baseline | Standard Error 0.36 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Body Weight for Treatment Naive Patients | -2.13 kg change from baseline | Standard Error 0.36 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Body Weight for Treatment Naive Patients | -2.27 kg change from baseline | Standard Error 0.37 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Body Weight for Treatment Naive Patients | -0.78 kg change from baseline | Standard Error 0.36 |
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).p-value: 0.80195% CI: [-0.88, 1.14]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).p-value: 0.361695% CI: [-1.48, 0.54]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).p-value: 0.017895% CI: [-2.23, -0.21]ANCOVA
Comparison: Model for Week 24 includes baseline weight (p\<0.0001), baseline HbA1c (p=0.0023) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0316), geographical region (p=0.0134), treatment (p=0.0031) as fixed effect(s).p-value: 0.000195% CI: [-2.97, -0.95]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients
Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients.
Time frame: Baseline and 24 Weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | -35.25 mg/dL change from baseline | Standard Error 2.53 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | -32.18 mg/dL change from baseline | Standard Error 2.52 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | -18.83 mg/dL change from baseline | Standard Error 2.47 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | -20.84 mg/dL change from baseline | Standard Error 2.5 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | -13.05 mg/dL change from baseline | Standard Error 2.59 |
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-23.37, -9.48]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-29.3, -15.1]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p\<0.0001) as fixed effect(s).p-value: 0.001595% CI: [-18.31, -4.37]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.6082) as linear covariate(s) and baseline eGFR (MDRD) (p=0.3685), geographical region (p=0.0104), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-26.21, -12.03]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients
Change from baseline in fasting plasma glucose at week 24 for Treatment Naive patients.
Time frame: Baseline and 24 Weeks
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | -29.55 mg/dL change from baseline | Standard Error 2.67 |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | -28.21 mg/dL change from baseline | Standard Error 2.66 |
| Metformin Background: Empagliflozin 25 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | -24.24 mg/dL change from baseline | Standard Error 2.68 |
| Metformin Background: Empagliflozin 10 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | -22.39 mg/dL change from baseline | Standard Error 2.69 |
| Metformin Background: Linagliptin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | -5.92 mg/dL change from baseline | Standard Error 2.68 |
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p\<0.0001) as fixed effect(s).p-value: 0.160595% CI: [-12.74, 2.11]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p\<0.0001) as fixed effect(s).p-value: 0.124695% CI: [-13.25, 1.61]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-31.06, -16.21]ANCOVA
Comparison: Model for Week 24 includes baseline fasting plasma glucose (p\<0.0001), baseline HbA1c (p=0.4591) as linear covariate(s) and baseline eGFR (MDRD) (p=0.7413), geographical region (p=0.1504), treatment (p\<0.0001) as fixed effect(s).p-value: <0.000195% CI: [-29.71, -14.88]ANCOVA
Secondary
Occurrence of Treat to Target Efficacy Response for Metformin Background Patients
Occurrence of the treat-to-target efficacy response for Metformin Background patients measured as HbA1c \< 7.0% after 24 weeks of treatment for patients with HbA1c \>=7.0% at baseline.
Time frame: 24 Weeks
Population: Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS- Metformin background patients randomised and treated who had a baseline (HbA1c\>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 61.8 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 57.8 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 25 mg | Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 32.6 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 10 mg | Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 28.0 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | 36.1 % of patients satisfying HbA1c <7.0% |
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: <0.000195% CI: [2.319, 7.573]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: <0.000195% CI: [2.474, 8.184]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: <0.000195% CI: [1.92, 6.363]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: 0.000595% CI: [1.562, 5.001]Regression, Logistic
Secondary
Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients
Occurrence of the treat-to-target efficacy response for Treatment Naive patients measured as HbA1c \< 7.0% after 24 weeks of treatment for patients with HbA1c \>=7.0% at baseline.
Time frame: 24 Weeks
Population: Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS-treatment naive patients randomised and treated who had a baseline (HbA1c\>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 55.4 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 62.3 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 25 mg | Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 41.5 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Empagliflozin 10 mg | Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 38.8 % of patients satisfying HbA1c <7.0% |
| Metformin Background: Linagliptin 5 mg | Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | 32.3 % of patients satisfying HbA1c <7.0% |
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: 0.022495% CI: [1.095, 3.274]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: 0.000195% CI: [1.697, 5.169]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: <0.000195% CI: [1.768, 5.314]Regression, Logistic
Comparison: Logistic regression includes treatment, baseline eGFR (MDRD), geographical region and baseline HbA1c.p-value: <0.000195% CI: [2.462, 7.522]Regression, Logistic