Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to investigate the efficacy, safety and pharmacokinetics of five doses of BI 10773 compared to placebo given for 12 weeks as add-on therapy to on going metformin therapy in patients with T2DM with insufficient glycemic control. In addition, there will be an open-label treatment arm with sitagliptin (JanuviaTM) as add-on therapy to metformin.
Interventions
DRUGBI 10773
DRUGplacebo
DRUGsitagliptin
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug 2. Stable metformin therapy of at least 1500 mg/day, or less if that is a maximum tolerated dose. 3. HbA1c at screening 6.5% to 9.0% for patients on metformin and one other antidiabetic drug, and HbA1c \>7.0% to 10% for patients on metformin only 4. HbA1c \>7.0% to 10.0% at Visit 2 (Start of Run-in) 5. Age \>=18 and \<80years 6. Body Mass Index (BMI) \<=40 kg/m2 7. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria
1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent 2. Impaired hepatic function 3. Renal insufficiency or impaired renal function 4. Diseases of the central nervous system or psychiatric disorders or clinically relevant neurological disorders that may interfere with participation in the trial 5. Chronic or clinically relevant acute infections 6. Current or chronic urogenital tract infection 7. History of clinically relevant allergy/hypersensitivity 8. Treatment with glitazones (e.g., rosiglitazone, pioglitazone), glucagon-like peptide (GLP-1) analogues, or insulin within 3 months prior to informed consent 9. Treatment with anti-obesity drugs within 3 months prior to informed consent 10. Treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent 11. Alcohol abuse or drug abuse 12. Treatment with an investigational drug within 2 months prior to informed consent 13. Women of child-bearing potential who are nursing or pregnant, or who are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to periodic pregnancy testing during participation in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c After 12 Weeks of Treatment | Baseline and 12 weeks | Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of HbA1c From Baseline Over Time | Baseline and weeks 4, 8 and 12 | Change of HbA1c from baseline over time. Results presented stem from a repeated measures analysis. |
| Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | Baseline and 12 weeks | Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%) based on logistic regression |
| Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | Baseline and 12 weeks | Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%) based on logistic regression |
| Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | Baseline and 12 weeks | Results for change of FPI from baseline at week 12 based on ANCOVA |
| Change of FPG From Baseline After 12 Weeks of Treatment | Baseline and 12 weeks | Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group. |
| Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | Baseline and 12 weeks | HOMA-%B (to assess insulin beta cell function) is defined as (20 x FPI)/(FPG-3.5), FPG in mg/dl. Results are based on ANCOVA. |
| Change of Body Weight After 12 Weeks of Treatment | Baseline and 12 weeks | Results for change of body weight after 12 weeks of treatment based on ANCOVA. |
| Trough Concentrations of Empagliflozin in Plasma | Days 28, 56 and 84 | (Pre-dose) trough concentrations of Empagliflozin in plasma, within 30 minutes of dosing. |
| Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | Baseline and 12 weeks | HOMA-IR (to assess insulin resistance) is defined as (FPI x FPG)/22.5. Results based on ANCOVA. |
Countries
Argentina, Austria, Czechia, Estonia, Finland, France, Germany, Hungary, Latvia, Norway, Romania, Russia, Slovakia, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients receive Placebo in tablets matching the Empagliflozin tablets in appearance once daily. | 71 |
| Empa 1 mg Patients receive 1 mg Empagliflozin in tablets once daily. | 71 |
| Empa 5 mg Patients receive 5 mg Empagliflozin in tablets once daily. | 71 |
| Empa 10 mg Patients receive 10 mg Empagliflozin in tablets once daily. | 71 |
| Empa 25 mg Patients receive 25 mg Empagliflozin in tablets once daily. | 70 |
| Empa 50 mg Patients receive 50 mg Empagliflozin in tablets once daily. | 70 |
| Sitag Patients receive 100 mg Sitagliptin (open-label) in tablets once daily. | 71 |
| Total | 495 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 4 | 0 | 3 | 0 |
| Overall Study | Lack of Efficacy | 3 | 1 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Other reason not defined above | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Empa 1 mg | Empa 5 mg | Empa 10 mg | Empa 25 mg | Empa 50 mg | Sitag | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.7 years STANDARD_DEVIATION 8.5 | 57.4 years STANDARD_DEVIATION 8.8 | 59.7 years STANDARD_DEVIATION 7.3 | 59.0 years STANDARD_DEVIATION 9 | 58.7 years STANDARD_DEVIATION 8.1 | 55.9 years STANDARD_DEVIATION 9.4 | 57.6 years STANDARD_DEVIATION 10.1 | 58.3 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 38 Participants | 30 Participants | 42 Participants | 38 Participants | 33 Participants | 31 Participants | 33 Participants | 245 Participants |
| Sex: Female, Male Male | 33 Participants | 41 Participants | 29 Participants | 33 Participants | 37 Participants | 39 Participants | 38 Participants | 250 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 71 | 2 / 71 | 2 / 71 | 7 / 71 | 4 / 70 | 3 / 70 | 4 / 71 |
| serious Total, serious adverse events | 2 / 71 | 0 / 71 | 3 / 71 | 1 / 71 | 2 / 70 | 3 / 70 | 0 / 71 |
Outcome results
Primary
Change From Baseline in HbA1c After 12 Weeks of Treatment
Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.
Time frame: Baseline and 12 weeks
Population: Full analysis set (FAS) consisting of all randomized patients who were treated with at least one dose of study drug and has a baseline measurement of the primary endpoint. The imputation method used was a modified last observation carried forward (LOCF) approach which used linear interpolation, LOCF and worst observation carried forward (WOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c After 12 Weeks of Treatment | 0.15 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 1 mg | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.09 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 5 mg | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.23 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 10 mg | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.56 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 25 mg | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.55 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 50 mg | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.49 percentage of HbA1c | Standard Error 0.08 |
| Sitagliptin OL | Change From Baseline in HbA1c After 12 Weeks of Treatment | -0.45 percentage of HbA1c | Standard Error 0.1 |
p-value: 0.022695% CI: [-0.44, -0.03]ANCOVA
p-value: 0.000295% CI: [-0.59, -0.18]ANCOVA
p-value: <0.000195% CI: [-0.91, -0.51]ANCOVA
p-value: <0.000195% CI: [-0.91, -0.5]ANCOVA
p-value: <0.000195% CI: [-0.84, -0.43]ANCOVA
Secondary
Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI)
Results for change of FPI from baseline at week 12 based on ANCOVA
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | 0.43 mU/L | Standard Error 0.57 |
| Empagliflozin 1 mg | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | 0.09 mU/L | Standard Error 0.59 |
| Empagliflozin 5 mg | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | -0.84 mU/L | Standard Error 0.58 |
| Empagliflozin 10 mg | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | -1.77 mU/L | Standard Error 0.58 |
| Empagliflozin 25 mg | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | -0.11 mU/L | Standard Error 0.59 |
| Empagliflozin 50 mg | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | -1.52 mU/L | Standard Error 0.57 |
| Sitagliptin OL | Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | 1.84 mU/L | Standard Error 0.58 |
Secondary
Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B)
HOMA-%B (to assess insulin beta cell function) is defined as (20 x FPI)/(FPG-3.5), FPG in mg/dl. Results are based on ANCOVA.
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 0.30 mU / mmol | Standard Error 2.7 |
| Empagliflozin 1 mg | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 0.08 mU / mmol | Standard Error 2.77 |
| Empagliflozin 5 mg | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 0.36 mU / mmol | Standard Error 2.76 |
| Empagliflozin 10 mg | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 1.55 mU / mmol | Standard Error 2.72 |
| Empagliflozin 25 mg | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 6.68 mU / mmol | Standard Error 2.78 |
| Empagliflozin 50 mg | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 4.01 mU / mmol | Standard Error 2.76 |
| Sitagliptin OL | Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | 12.38 mU / mmol | Standard Error 2.75 |
Secondary
Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR)
HOMA-IR (to assess insulin resistance) is defined as (FPI x FPG)/22.5. Results based on ANCOVA.
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | 0.23 mU/L x mmol/L | Standard Error 0.26 |
| Empagliflozin 1 mg | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | -0.11 mU/L x mmol/L | Standard Error 0.27 |
| Empagliflozin 5 mg | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | -0.60 mU/L x mmol/L | Standard Error 0.26 |
| Empagliflozin 10 mg | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | -1.04 mU/L x mmol/L | Standard Error 0.26 |
| Empagliflozin 25 mg | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | -0.52 mU/L x mmol/L | Standard Error 0.27 |
| Empagliflozin 50 mg | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | -1.10 mU/L x mmol/L | Standard Error 0.27 |
| Sitagliptin OL | Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | 0.48 mU/L x mmol/L | Standard Error 0.26 |
Secondary
Change of Body Weight After 12 Weeks of Treatment
Results for change of body weight after 12 weeks of treatment based on ANCOVA.
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change of Body Weight After 12 Weeks of Treatment | -1.16 kg | Standard Error 0.31 |
| Empagliflozin 1 mg | Change of Body Weight After 12 Weeks of Treatment | -1.55 kg | Standard Error 0.31 |
| Empagliflozin 5 mg | Change of Body Weight After 12 Weeks of Treatment | -2.28 kg | Standard Error 0.31 |
| Empagliflozin 10 mg | Change of Body Weight After 12 Weeks of Treatment | -2.74 kg | Standard Error 0.31 |
| Empagliflozin 25 mg | Change of Body Weight After 12 Weeks of Treatment | -2.56 kg | Standard Error 0.31 |
| Empagliflozin 50 mg | Change of Body Weight After 12 Weeks of Treatment | -2.85 kg | Standard Error 0.32 |
| Sitagliptin OL | Change of Body Weight After 12 Weeks of Treatment | -0.84 kg | Standard Error 0.31 |
Secondary
Change of FPG From Baseline After 12 Weeks of Treatment
Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.
Time frame: Baseline and 12 weeks
Population: FAS using modified LOCF imputation method
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change of FPG From Baseline After 12 Weeks of Treatment | 4.75 mg/dL | Standard Error 3.48 |
| Empagliflozin 1 mg | Change of FPG From Baseline After 12 Weeks of Treatment | -1.70 mg/dL | Standard Error 3.49 |
| Empagliflozin 5 mg | Change of FPG From Baseline After 12 Weeks of Treatment | -15.84 mg/dL | Standard Error 3.45 |
| Empagliflozin 10 mg | Change of FPG From Baseline After 12 Weeks of Treatment | -22.14 mg/dL | Standard Error 3.49 |
| Empagliflozin 25 mg | Change of FPG From Baseline After 12 Weeks of Treatment | -26.83 mg/dL | Standard Error 3.47 |
| Empagliflozin 50 mg | Change of FPG From Baseline After 12 Weeks of Treatment | -27.91 mg/dL | Standard Error 3.47 |
| Sitagliptin OL | Change of FPG From Baseline After 12 Weeks of Treatment | -12.92 mg/dL | Standard Error 4.73 |
Secondary
Change of HbA1c From Baseline Over Time
Change of HbA1c from baseline over time. Results presented stem from a repeated measures analysis.
Time frame: Baseline and weeks 4, 8 and 12
Population: FAS. Imputation method used was the classical LOCF (CLOCF) approach which uses always the last available value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change of HbA1c From Baseline Over Time | Week 12 | 0.12 percentage of HbA1c | Standard Error 0.08 |
| Placebo | Change of HbA1c From Baseline Over Time | Week 8 | 0.05 percentage of HbA1c | Standard Error 0.07 |
| Placebo | Change of HbA1c From Baseline Over Time | Week 4 | 0.02 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 1 mg | Change of HbA1c From Baseline Over Time | Week 8 | -0.14 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 1 mg | Change of HbA1c From Baseline Over Time | Week 4 | -0.12 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 1 mg | Change of HbA1c From Baseline Over Time | Week 12 | -0.08 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 5 mg | Change of HbA1c From Baseline Over Time | Week 12 | -0.27 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 5 mg | Change of HbA1c From Baseline Over Time | Week 4 | -0.16 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 5 mg | Change of HbA1c From Baseline Over Time | Week 8 | -0.30 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 10 mg | Change of HbA1c From Baseline Over Time | Week 8 | -0.57 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 10 mg | Change of HbA1c From Baseline Over Time | Week 4 | -0.32 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 10 mg | Change of HbA1c From Baseline Over Time | Week 12 | -0.57 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 25 mg | Change of HbA1c From Baseline Over Time | Week 8 | -0.52 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 25 mg | Change of HbA1c From Baseline Over Time | Week 4 | -0.31 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 25 mg | Change of HbA1c From Baseline Over Time | Week 12 | -0.59 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 50 mg | Change of HbA1c From Baseline Over Time | Week 4 | -0.36 percentage of HbA1c | Standard Error 0.06 |
| Empagliflozin 50 mg | Change of HbA1c From Baseline Over Time | Week 12 | -0.50 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 50 mg | Change of HbA1c From Baseline Over Time | Week 8 | -0.53 percentage of HbA1c | Standard Error 0.07 |
| Sitagliptin OL | Change of HbA1c From Baseline Over Time | Week 12 | -0.45 percentage of HbA1c | Standard Error 0.08 |
| Sitagliptin OL | Change of HbA1c From Baseline Over Time | Week 8 | -0.40 percentage of HbA1c | Standard Error 0.07 |
| Sitagliptin OL | Change of HbA1c From Baseline Over Time | Week 4 | -0.26 percentage of HbA1c | Standard Error 0.06 |
Secondary
Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment
Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%) based on logistic regression
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 15.5 percentage of participants |
| Empagliflozin 1 mg | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 23.9 percentage of participants |
| Empagliflozin 5 mg | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 21.1 percentage of participants |
| Empagliflozin 10 mg | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 38.0 percentage of participants |
| Empagliflozin 25 mg | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 37.1 percentage of participants |
| Empagliflozin 50 mg | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 35.7 percentage of participants |
| Sitagliptin OL | Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | 33.8 percentage of participants |
Secondary
Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment
Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%) based on logistic regression
Time frame: Baseline and 12 weeks
Population: FAS (CLOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 21.1 percentage of participants |
| Empagliflozin 1 mg | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 31.0 percentage of participants |
| Empagliflozin 5 mg | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 40.8 percentage of participants |
| Empagliflozin 10 mg | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 60.6 percentage of participants |
| Empagliflozin 25 mg | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 60.0 percentage of participants |
| Empagliflozin 50 mg | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 48.6 percentage of participants |
| Sitagliptin OL | Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | 53.5 percentage of participants |
Secondary
Trough Concentrations of Empagliflozin in Plasma
(Pre-dose) trough concentrations of Empagliflozin in plasma, within 30 minutes of dosing.
Time frame: Days 28, 56 and 84
Population: All patients who received at least one dose of Empagliflozin and have some Pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough Concentrations of Empagliflozin in Plasma | Day 28 (N=58, 65, 62, 58, 63) | 3.19 nmol/L | Geometric Coefficient of Variation 88.8 |
| Placebo | Trough Concentrations of Empagliflozin in Plasma | Day 84 (N=53, 61, 59, 57, 57) | 2.87 nmol/L | Geometric Coefficient of Variation 80.1 |
| Placebo | Trough Concentrations of Empagliflozin in Plasma | Day 56 (N=56, 64, 64, 61, 61) | 2.93 nmol/L | Geometric Coefficient of Variation 69.6 |
| Empagliflozin 1 mg | Trough Concentrations of Empagliflozin in Plasma | Day 56 (N=56, 64, 64, 61, 61) | 11.5 nmol/L | Geometric Coefficient of Variation 63.2 |
| Empagliflozin 1 mg | Trough Concentrations of Empagliflozin in Plasma | Day 28 (N=58, 65, 62, 58, 63) | 13.1 nmol/L | Geometric Coefficient of Variation 79.4 |
| Empagliflozin 1 mg | Trough Concentrations of Empagliflozin in Plasma | Day 84 (N=53, 61, 59, 57, 57) | 11.2 nmol/L | Geometric Coefficient of Variation 69.6 |
| Empagliflozin 5 mg | Trough Concentrations of Empagliflozin in Plasma | Day 56 (N=56, 64, 64, 61, 61) | 23.0 nmol/L | Geometric Coefficient of Variation 93.8 |
| Empagliflozin 5 mg | Trough Concentrations of Empagliflozin in Plasma | Day 28 (N=58, 65, 62, 58, 63) | 27.3 nmol/L | Geometric Coefficient of Variation 127 |
| Empagliflozin 5 mg | Trough Concentrations of Empagliflozin in Plasma | Day 84 (N=53, 61, 59, 57, 57) | 23.4 nmol/L | Geometric Coefficient of Variation 85.1 |
| Empagliflozin 10 mg | Trough Concentrations of Empagliflozin in Plasma | Day 28 (N=58, 65, 62, 58, 63) | 92.5 nmol/L | Geometric Coefficient of Variation 111 |
| Empagliflozin 10 mg | Trough Concentrations of Empagliflozin in Plasma | Day 84 (N=53, 61, 59, 57, 57) | 71.0 nmol/L | Geometric Coefficient of Variation 111 |
| Empagliflozin 10 mg | Trough Concentrations of Empagliflozin in Plasma | Day 56 (N=56, 64, 64, 61, 61) | 75.4 nmol/L | Geometric Coefficient of Variation 140 |
| Empagliflozin 25 mg | Trough Concentrations of Empagliflozin in Plasma | Day 56 (N=56, 64, 64, 61, 61) | 119 nmol/L | Geometric Coefficient of Variation 85.5 |
| Empagliflozin 25 mg | Trough Concentrations of Empagliflozin in Plasma | Day 28 (N=58, 65, 62, 58, 63) | 119 nmol/L | Geometric Coefficient of Variation 78.7 |
| Empagliflozin 25 mg | Trough Concentrations of Empagliflozin in Plasma | Day 84 (N=53, 61, 59, 57, 57) | 112 nmol/L | Geometric Coefficient of Variation 79.6 |