Diabetes Mellitus, Type 2, Obesity
Conditions
Brief summary
This trial will evaluate use of BI 10773 as add-on to insulin regimen alone or with metformin in patients with typr 2 diabetes. Both lowering glucose and HbA1c and reducing the use of insulin in this population would provide significant new information for the BI 10773 use and would offer a potential new therapeutic option in this population.
Interventions
DRUGPlacebo
Placebo matching BI 10773 low dose
DRUGBI 10773
BI 10773 low dose 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 T2DM prior to informed consent 2. Male and female patients on diet and exercise regimen who are pre-treated with multiple daily injections (MDI) of insulin alone or in combination with immediate or extended release metformin 3. Stable metformin therapy: daily dose \>=1500 mg/day or maximum tolerated dose 4. HbA1c \>=7.5% and \<=10% at 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 2. Any contraindications to metformin according to the local label 3. Acute coronary syndrome, stroke or TIA within 3 months prior to informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c After 18 Weeks of Treatment | Baseline and 18 weeks | The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin Dose After 52 Weeks of Treatment | Baseline and 52 weeks | The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment |
| Change From Baseline in Body Weight After 52 Weeks of Treatment | Baseline and 52 weeks | The secondary endpoint was the change from baseline in body weight after 52 weeks of treatment |
| Change From Baseline in HbA1c After 52 Weeks of Treatment | Baseline and 52 weeks | The secondary endpoint was the change from baseline in HbA1c after 52 weeks of treatment |
Countries
Belgium, Bulgaria, Colombia, Czechia, Finland, France, Germany, Guatemala, Mexico, Peru, Russia, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily | 188 |
| Empagliflozin 10 mg Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily | 186 |
| Empagliflozin 25 mg Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily | 189 |
| Total | 563 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 5 | 4 |
| Overall Study | Not treated | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 24 | 22 | 16 |
Baseline characteristics
| Characteristic | Placebo | Empagliflozin 10 mg | Empagliflozin 25 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 10.1 | 56.7 years STANDARD_DEVIATION 8.7 | 58.0 years STANDARD_DEVIATION 9.4 | 56.7 years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 113 Participants | 89 Participants | 105 Participants | 307 Participants |
| Sex: Female, Male Male | 75 Participants | 97 Participants | 84 Participants | 256 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 | 146 / 188 | 135 / 186 | 140 / 189 |
| serious Total, serious adverse events | 22 / 188 | 20 / 186 | 22 / 189 |
Outcome results
Primary
Change From Baseline in HbA1c After 18 Weeks of Treatment
The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment.
Time frame: Baseline and 18 weeks
Population: The analysis was conducted on the full analysis set (FAS) of patients. Values after start of antidiabetic rescue therapy (week 18 definition) were set to missing and last observation carried forward (LOCF-18) was used for imputation of missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c After 18 Weeks of Treatment | -0.50 percentage of HbA1c | Standard Error 0.05 |
| Empagliflozin 10 mg | Change From Baseline in HbA1c After 18 Weeks of Treatment | -0.94 percentage of HbA1c | Standard Error 0.05 |
| Empagliflozin 25 mg | Change From Baseline in HbA1c After 18 Weeks of Treatment | -1.02 percentage of HbA1c | Standard Error 0.05 |
Comparison: For the primary endpoint, the testing of the superiority hypothesis versus placebo was:~Hypothesis test:~H0: No difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebop-value: <0.000197.5% CI: [-0.61, -0.27]ANCOVA
Comparison: For the primary endpoint, the testing of the superiority hypothesis versus placebo was:~H0: No difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 25 mg and placebo Ha: A difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 25 mg and placebop-value: <0.000197.5% CI: [-0.69, -0.35]ANCOVA
Secondary
Change From Baseline in Body Weight After 52 Weeks of Treatment
The secondary endpoint was the change from baseline in body weight after 52 weeks of treatment
Time frame: Baseline and 52 weeks
Population: Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight After 52 Weeks of Treatment | 0.44 kg | Standard Error 0.36 |
| Empagliflozin 10 mg | Change From Baseline in Body Weight After 52 Weeks of Treatment | -1.95 kg | Standard Error 0.36 |
| Empagliflozin 25 mg | Change From Baseline in Body Weight After 52 Weeks of Treatment | -2.04 kg | Standard Error 0.36 |
Comparison: Hypothesis test:~H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebop-value: <0.000197.5% CI: [-3.54, -1.24]ANCOVA
Comparison: hypothesis test: H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebo Ha: A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebop-value: <0.000197.5% CI: [-3.63, -1.33]ANCOVA
Secondary
Change From Baseline in HbA1c After 52 Weeks of Treatment
The secondary endpoint was the change from baseline in HbA1c after 52 weeks of treatment
Time frame: Baseline and 52 weeks
Population: Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c After 52 Weeks of Treatment | -0.81 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 10 mg | Change From Baseline in HbA1c After 52 Weeks of Treatment | -1.18 percentage of HbA1c | Standard Error 0.08 |
| Empagliflozin 25 mg | Change From Baseline in HbA1c After 52 Weeks of Treatment | -1.27 percentage of HbA1c | Standard Error 0.08 |
Comparison: H0: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo \>0.3 Ha: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo ≤0.3p-value: <0.000197.5% CI: [-0.62, -0.13]ANCOVA
Comparison: Hypothesis test:~H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebop-value: 0.000597.5% CI: [-0.62, -0.13]ANCOVA
Comparison: H013: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo \>0.3 Ha13: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo ≤0.3p-value: <0.000197.5% CI: [-0.7, -0.22]ANCOVA
Comparison: Hypothesis test:~H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebop-value: <0.000197.5% CI: [-0.7, -0.22]ANCOVA
Secondary
Change From Baseline in Insulin Dose After 52 Weeks of Treatment
The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment
Time frame: Baseline and 52 weeks
Population: Per Protocol Set-patients in FAS without important protocol violations leading to exclusion, completed minimum treatment of 357 days and did not prematurely discontinue. Values after start of antidiabetic rescue therapy (week 52 definition) were set to missing and last observation carried forward (LOCF-52) was used for imputation of missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Insulin Dose After 52 Weeks of Treatment | 10.16 IU/day | Standard Error 2.16 |
| Empagliflozin 10 mg | Change From Baseline in Insulin Dose After 52 Weeks of Treatment | 1.33 IU/day | Standard Error 2.13 |
| Empagliflozin 25 mg | Change From Baseline in Insulin Dose After 52 Weeks of Treatment | -1.06 IU/day | Standard Error 2.14 |
Comparison: Hypothesis test:~H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebop-value: 0.00497.5% CI: [-15.69, -1.97]ANCOVA
Comparison: Hypothesis test:~H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebop-value: 0.000397.5% CI: [-18.09, -4.36]ANCOVA