Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to investigate the efficacy, safety and tolerability of BI 10773 at two different doses compared to placebo during long term treatment (78 weeks) in combination with basal insulin in patients with type 2 diabetes mellitus with insufficient glycaemic control.
Interventions
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. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation 2. Male and female patients with a diagnosis of Type 2 Diabetes Mellitus treated with a stable dose of basal insulin with or without concomitant metformin and / or sulfonylurea. 3. Glycosylated hemoglobin A1c (Type A, subtype 1c) of \>7.0% and \< or = 10% at Visit 1 (screening) 4. Suitability for trial participation according to investigator's judgment (evaluating all alternative treatment options and in consideration of the patient completing the study) 5. Age \> or =18 years at Visit 1 (screening) 6. BMI \< or = 45 kg/m2 (Body Mass Index) at Visit 1 (screening)
Exclusion criteria
1. Patients with poorly controlled hyperglycemia 2. Frequent (at the discretion of the investigator) episodes of hypoglycemic events on basal insulin therapy 3. MI, stroke, or TIA within 3 months prior to obtaining informed consent 4. Impaired hepatic or renal function; gastric surgery; cancer within the last 5 years; blood dyscrasias 6\. Treatment with other anti-diabetics, anti-obesity medications, steroids or thyroid hormones, participation in another trial with an investigational drug 7. Pre-menopausal women on insufficient birth control 8. Alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment | Baseline and 18 weeks | Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | Baseline and 18, 54 and 78 weeks | Patients that had a reduction in HbA1c of at least 0.5% from baseline to 18, 54 and 78 weeks of treatment |
| Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | Baseline, 18, 54 and 78 weeks | Change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment |
| Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | Baseline, 18, 54 and 78 weeks | Percent change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment |
| Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | Baseline, 54 and 78 weeks | Change from baseline in basal insulin dose/day after 54 and 78 weeks of treatment |
| Change From Baseline in Body Weight at Follow-up | Baseline and 82 weeks | Change from baseline in body weight at follow up (82 weeks) |
| Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Baseline, 54 and 78 weeks | Change from baseline in HbA1c after 54 and 78 weeks of treatment |
| The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | Baseline, 18, 54 and 78 weeks | The occurrence of treat to target efficacy response, that is an HbA1c under treatment of \<7.0% After 18, 54, and 78 weeks of treatment |
| Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | Baseline, 18, 54, 78 weeks | Change from baseline in body weight after 18, 54 and 78 weeks of treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Hypoglycemic Events | During the course of the study (82 weeks) | Confirmed hypoglycemic events refer to all hypoglycemic events that had a glucose value ≤70 ml/dL or where assistance was required. Symptomatic hypoglycemic events were to be reported as adverse events. Investigator-defined hypoglycaemia adverse events include all events that investigator marked as 'Hypoglycaemic event' in CRFs, regardless of the reported term or blood glucose value. It may include hypoglycemia itself as reported term or any other symptoms that that investigator may have attributed to hypoglycemia (e.g. dizziness, hyperhidrosis, and asthenia). |
Countries
Denmark, France, Ireland, Portugal, South Korea, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Oral Placebo | 170 |
| Empagliflozin 10 mg Empagliflozin 10 mg orally once daily | 169 |
| Empagliflozin 25 mg Empagliflozin 25 mg orally once daily | 155 |
| Total | 494 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| After Week 18 Follow-up | Adverse Event | 8 | 6 | 13 |
| After Week 18 Follow-up | Lack of Efficacy | 1 | 0 | 0 |
| After Week 18 Follow-up | Lost to Follow-up | 5 | 3 | 0 |
| After Week 18 Follow-up | Other reason not defined above | 2 | 3 | 12 |
| After Week 18 Follow-up | Protocol Violation | 1 | 1 | 1 |
| After Week 18 Follow-up | Withdrawal by Subject | 6 | 3 | 0 |
| After Week 78 Follow-up | Adverse Event | 14 | 18 | 21 |
| After Week 78 Follow-up | Lack of Efficacy | 4 | 0 | 0 |
| After Week 78 Follow-up | Lost to Follow-up | 11 | 6 | 4 |
| After Week 78 Follow-up | Other reason not defined above | 5 | 5 | 16 |
| After Week 78 Follow-up | Protocol Violation | 9 | 1 | 2 |
| After Week 78 Follow-up | Withdrawal by Subject | 9 | 8 | 1 |
Baseline characteristics
| Characteristic | Placebo | Empagliflozin 10 mg | Empagliflozin 25 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 9.4 | 58.6 years STANDARD_DEVIATION 9.8 | 59.9 years STANDARD_DEVIATION 10.5 | 58.8 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 80 Participants | 76 Participants | 62 Participants | 218 Participants |
| Sex: Female, Male Male | 90 Participants | 93 Participants | 93 Participants | 276 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 115 / 170 | 110 / 169 | 95 / 155 |
| serious Total, serious adverse events | 28 / 170 | 28 / 169 | 28 / 155 |
Outcome results
Primary
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment
Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment
Time frame: Baseline and 18 weeks
Population: FAS18-completers-included FAS patients not prematurely discontinue prior to Week 18, completed required minimum treatment duration, and had an on treatment HbA1c value within Week 18 time window. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF-18) was used for imputation.~(LOCF-18)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment | 0.03 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 10 mg | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment | -0.58 percentage of HbA1c | Standard Error 0.07 |
| Empagliflozin 25 mg | Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment | -0.75 percentage of HbA1c | Standard Error 0.08 |
Comparison: The null and alternative hypotheses to be tested:~* H0,1: No difference in change from baseline to Week 18 in HbA1c between empagliflozin 10 mg and placebo~* H1,1: A difference in change from baseline to Week 18 in HbA1c between empagliflozin 10 mg and placebop-value: <0.000197.5% CI: [-0.78, -0.33]ANCOVA
Comparison: The null and alternative hypotheses to be tested:~* H0,2: No difference in change from baseline to Week 18 in HbA1c between empagliflozin 25 mg and placebo~* H1,2: A difference in change from baseline to Week 18 in HbA1c between empagliflozin 25 mg and placebop-value: <0.000197.5% CI: [-0.93, -0.47]ANCOVA
Secondary
Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment
Change from baseline in basal insulin dose/day after 54 and 78 weeks of treatment
Time frame: Baseline, 54 and 78 weeks
Population: FAS (OC-78) for week 54 FAS78-completers (LOCF-78) for week 78 - Values after start of antidiabetic rescue therapy except changes in basal insulin dose were set to missing and last observation carried forward (LOCF) was used for imputation of missing values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 54 (N=112,122,104) | 5.39 IU | Standard Error 1.6 |
| Placebo | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 78 | 4.79 IU | Standard Error 2.06 |
| Empagliflozin 10 mg | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 54 (N=112,122,104) | -1.20 IU | Standard Error 1.4 |
| Empagliflozin 10 mg | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 78 | -0.70 IU | Standard Error 1.85 |
| Empagliflozin 25 mg | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 54 (N=112,122,104) | -1.12 IU | Standard Error 1.27 |
| Empagliflozin 25 mg | Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment | week 78 | -0.39 IU | Standard Error 1.06 |
Comparison: Empagliflozin versus Placebo 10 mg at 54 weeksp-value: 0.021395% CI: [-10.32, -0.84]Mixed Models Analysis
Comparison: Empagliflozin versus Placebo 25 mg at 54 weeksp-value: 0.023795% CI: [-10.62, -0.77]Mixed Models Analysis
Comparison: Empagliflozin versus Placebo 10 mg at 78 weeks~H0,1a: No difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 10 mg and placebo H1,1a: A difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 10 mg and placebop-value: 0.002497.5% CI: [-11.56, -1.77]ANCOVA
Comparison: Empagliflozin versus Placebo 25 mg at 78 weeks~H0,1a: No difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 25 mg and placebo H1,1a: A difference in change from baseline to Week 78 in basal insulin dose between Empagliflozin 25 mg and placebop-value: 0.00997.5% CI: [-11, -0.85]ANCOVA
Secondary
Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment
Change from baseline in body weight after 18, 54 and 78 weeks of treatment
Time frame: Baseline, 18, 54, 78 weeks
Population: FAS (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 54 weeks (N=114,120,106) | -0.52 kg | Standard Error 0.32 |
| Placebo | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 18 weeks | -0.04 kg | Standard Error 0.21 |
| Placebo | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 78 weeks (N=100,113,96) | 1.12 kg | Standard Error 1.28 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 54 weeks (N=114,120,106) | -2.28 kg | Standard Error 0.33 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 18 weeks | -2.06 kg | Standard Error 0.22 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 78 weeks (N=100,113,96) | -2.61 kg | Standard Error 0.31 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 18 weeks | -0.91 kg | Standard Error 1.27 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 78 weeks (N=100,113,96) | -1.99 kg | Standard Error 0.32 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment | 54 weeks (N=114,120,106) | -2.23 kg | Standard Error 0.35 |
Comparison: Change from BL at week 18 - Empagliflozin 10 mg vs Placebop-value: 0.03295% CI: [-3.9, -0.18]Mixed Models Analysis
Comparison: Change from BL at week 18 - Empagliflozin 25 mg vs Placebop-value: 0.381895% CI: [-2.81, 1.08]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 10 mg vs Placebop-value: <0.000195% CI: [-2.89, -1.05]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 25 mg vs Placebop-value: <0.000195% CI: [-3.13, -1.22]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 10 mg vs Placebop-value: 0.001295% CI: [-5.81, -1.45]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 25 mg vs Placebop-value: 0.007395% CI: [-5.39, -0.85]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight at Follow-up
Change from baseline in body weight at follow up (82 weeks)
Time frame: Baseline and 82 weeks
Population: FAS-FU (OR)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Follow-up | Follow-up change from baseline | 0.92 kg | Standard Deviation 12.2 |
| Placebo | Change From Baseline in Body Weight at Follow-up | Follow-up | 90.56 kg | Standard Deviation 25.87 |
| Placebo | Change From Baseline in Body Weight at Follow-up | Change from last value on treatment N=111,118,109 | -0.23 kg | Standard Deviation 16.84 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight at Follow-up | Follow-up change from baseline | -2.02 kg | Standard Deviation 4.04 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight at Follow-up | Follow-up | 90.44 kg | Standard Deviation 19.35 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight at Follow-up | Change from last value on treatment N=111,118,109 | 0.62 kg | Standard Deviation 2.11 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight at Follow-up | Follow-up | 93.98 kg | Standard Deviation 20.87 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight at Follow-up | Change from last value on treatment N=111,118,109 | 1.34 kg | Standard Deviation 1.9 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight at Follow-up | Follow-up change from baseline | -1.05 kg | Standard Deviation 3.96 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment
Change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment
Time frame: Baseline, 18, 54 and 78 weeks
Population: FAS observed cases (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 Change from BL (N=103,111,99) | 0.91 mg/dL | Standard Error 5.08 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 Change from BL | 9.81 mg/dL | Standard Error 5.48 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 Change from BL (N=92,104,92) | -5.53 mg/dL | Standard Error 4.95 |
| Empagliflozin 10 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 Change from BL (N=103,111,99) | -9.59 mg/dL | Standard Error 4.69 |
| Empagliflozin 10 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 Change from BL | -14.79 mg/dL | Standard Error 3.93 |
| Empagliflozin 10 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 Change from BL (N=92,104,92) | -7.75 mg/dL | Standard Error 4.66 |
| Empagliflozin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 Change from BL | -27.03 mg/dL | Standard Error 3.92 |
| Empagliflozin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 Change from BL (N=92,104,92) | -21.62 mg/dL | Standard Error 5.13 |
| Empagliflozin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 Change from BL (N=103,111,99) | -23.75 mg/dL | Standard Error 4.62 |
Comparison: Change from BL at week 18 - Empagliflozin 10 mg vs Placebop-value: <0.000195% CI: [-37.54, -19.27]Mixed Models Analysis
Comparison: Change from BL at week 18 - Empagliflozin 25 mg vs Placebo at 18 weeksp-value: <0.000195% CI: [-43.67, -24.76]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 10 mg vs Placebo at 18 weeksp-value: 0.032895% CI: [-20.62, -0.89]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 25 mg vs Placebop-value: 0.000295% CI: [-29.31, -9.01]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 10 mg vs Placebop-value: 0.321695% CI: [-15.01, 4.94]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 25 mg vs Placebop-value: 0.022995% CI: [-22.24, -1.67]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment
Change from baseline in HbA1c after 54 and 78 weeks of treatment
Time frame: Baseline, 54 and 78 weeks
Population: Week 54 - FAS (OC-78) Week 78 - FAS78-completers (LOCF-78)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 54 (N=113,121,107) | -0.06 percentage of HbA1c | Standard Error 0.08 |
| Placebo | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 78 (N=112,127,110) | -0.05 percentage of HbA1c | Standard Error 0.1 |
| Empagliflozin 10 mg | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 54 (N=113,121,107) | -0.59 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 10 mg | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 78 (N=112,127,110) | -0.51 percentage of HbA1c | Standard Error 0.09 |
| Empagliflozin 25 mg | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 54 (N=113,121,107) | -0.84 percentage of HbA1c | Standard Error 0.09 |
| Empagliflozin 25 mg | Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment | Week 78 (N=112,127,110) | -0.68 percentage of HbA1c | Standard Error 0.09 |
Comparison: Change from BL at week 54 - Empagliflozin 10 mg vs Placebop-value: <0.000195% CI: [-0.68, -0.26]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 25 mg vs Placebop-value: <0.000195% CI: [-0.95, -0.52]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 10 mg vs Placebo~H0,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 10 mg and placebo ≥0.3% H1,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 10 mg and placebo \<0.3%p-value: 0.000197.5% CI: [-0.73, -0.19]ANCOVA
Comparison: Change from BL at week 78 - Empagliflozin 25 mg vs Placebo~H0,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 25 mg and placebo ≥0.3% H1,1b: The change from baseline to Week 78 in HbA1c between empagliflozin 25 mg and placebo \<0.3%p-value: <0.000197.5% CI: [-0.9, -0.34]ANCOVA
Secondary
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment
Patients that had a reduction in HbA1c of at least 0.5% from baseline to 18, 54 and 78 weeks of treatment
Time frame: Baseline and 18, 54 and 78 weeks
Population: FAS with non-completers considered failure (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 78 weeks | 27 participants |
| Placebo | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 18 weeks | 27 participants |
| Placebo | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 54 weeks | 30 participants |
| Empagliflozin 10 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 78 weeks | 59 participants |
| Empagliflozin 10 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 18 weeks | 85 participants |
| Empagliflozin 10 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 54 weeks | 72 participants |
| Empagliflozin 25 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 78 weeks | 61 participants |
| Empagliflozin 25 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 18 weeks | 73 participants |
| Empagliflozin 25 mg | Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment | 54 weeks | 69 participants |
Comparison: Empagliflozin 10 mg vs Placebo at 18 weeksp-value: <0.000195% CI: [3.262, 9.334]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 18 weeksp-value: <0.000195% CI: [2.859, 8.338]Regression, Logistic
Comparison: Empagliflozin 10 mg vs Placebo at 54 weeksp-value: <0.000195% CI: [2.077, 5.802]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 54 weeksp-value: <0.000195% CI: [2.268, 6.451]Regression, Logistic
Comparison: Empagliflozin 10 mg vs Placebo at 78 weeksp-value: 0.000295% CI: [1.639, 4.789]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 78 weeksp-value: <0.000195% CI: [2.051, 6.066]Regression, Logistic
Secondary
Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment
Percent change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment
Time frame: Baseline, 18, 54 and 78 weeks
Population: FAS (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 % CHG (N=103,111,99) | 9.67 percentage of Change from BL in FPG | Standard Error 5.58 |
| Placebo | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 % CHG | 19.02 percentage of Change from BL in FPG | Standard Error 6.32 |
| Placebo | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 % CHG (N=92,104,92) | 4.75 percentage of Change from BL in FPG | Standard Error 5.67 |
| Empagliflozin 10 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 % CHG (N=103,111,99) | 0.67 percentage of Change from BL in FPG | Standard Error 4.05 |
| Empagliflozin 10 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 % CHG | -2.80 percentage of Change from BL in FPG | Standard Error 3.17 |
| Empagliflozin 10 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 % CHG (N=92,104,92) | 2.43 percentage of Change from BL in FPG | Standard Error 4.18 |
| Empagliflozin 25 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 18 % CHG | -13.43 percentage of Change from BL in FPG | Standard Error 2.39 |
| Empagliflozin 25 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 78 % CHG (N=92,104,92) | -9.52 percentage of Change from BL in FPG | Standard Error 3.4 |
| Empagliflozin 25 mg | Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment | week 54 % CHG (N=103,111,99) | -11.59 percentage of Change from BL in FPG | Standard Error 3.04 |
Comparison: Change from BL at week 18 - Empagliflozin 10 mg vs Placebop-value: <0.000195% CI: [-35.38, -14.86]Mixed Models Analysis
Comparison: Change from BL at week 18 - Empagliflozin 25 mg vs Placebop-value: <0.000195% CI: [-41.62, -20.39]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 10 mg vs Placebop-value: <0.048495% CI: [-20.33, -0.07]Mixed Models Analysis
Comparison: Change from BL at week 54 - Empagliflozin 25 mg vs Placebop-value: 0.000395% CI: [-29.84, -8.99]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 10 mg vs Placebop-value: 0.351795% CI: [-14.71, 5.25]Mixed Models Analysis
Comparison: Change from BL at week 78 - Empagliflozin 25 mg vs Placebop-value: 0.018595% CI: [-22.69, -2.1]Mixed Models Analysis
Secondary
The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment
The occurrence of treat to target efficacy response, that is an HbA1c under treatment of \<7.0% After 18, 54, and 78 weeks of treatment
Time frame: Baseline, 18, 54 and 78 weeks
Population: FAS (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 54 weeks | 14 participants |
| Placebo | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 18 weeks | 9 participants |
| Placebo | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 78 weeks | 11 participants |
| Empagliflozin 10 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 54 weeks | 23 participants |
| Empagliflozin 10 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 18 weeks | 30 participants |
| Empagliflozin 10 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 78 weeks | 20 participants |
| Empagliflozin 25 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 18 weeks | 30 participants |
| Empagliflozin 25 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 78 weeks | 27 participants |
| Empagliflozin 25 mg | The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment | 54 weeks | 27 participants |
Comparison: Empagliflozin 10 mg vs Placebo at 18 weeksp-value: 0.000595% CI: [1.846, 9.088]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 18 weeksp-value: 0.000295% CI: [2.083, 10.321]Regression, Logistic
Comparison: Empagliflozin 10 mg vs Placebo at 54 weeksp-value: 0.124895% CI: [0.856, 3.575]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 54 weeksp-value: 0.013295% CI: [1.203, 4.879]Regression, Logistic
Comparison: Empagliflozin 10 mg vs Placebo at 78 weeksp-value: 0.098695% CI: [0.884, 4.256]Regression, Logistic
Comparison: Empagliflozin 25 mg vs Placebo at 78 weeksp-value: 0.002495% CI: [1.518, 6.911]Regression, Logistic
Other Pre-specified
Confirmed Hypoglycemic Events
Confirmed hypoglycemic events refer to all hypoglycemic events that had a glucose value ≤70 ml/dL or where assistance was required. Symptomatic hypoglycemic events were to be reported as adverse events. Investigator-defined hypoglycaemia adverse events include all events that investigator marked as 'Hypoglycaemic event' in CRFs, regardless of the reported term or blood glucose value. It may include hypoglycemia itself as reported term or any other symptoms that that investigator may have attributed to hypoglycemia (e.g. dizziness, hyperhidrosis, and asthenia).
Time frame: During the course of the study (82 weeks)
Population: Treated set (TS). Treatment assignment as first medication taken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Confirmed Hypoglycemic Events | 60 participants |
| Empagliflozin 10 mg | Confirmed Hypoglycemic Events | 61 participants |
| Empagliflozin 25 mg | Confirmed Hypoglycemic Events | 56 participants |