Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the study is to investigate the long-term safety and efficacy of BI 10773 given for 52 weeks as add-on therapy to one oral antidiabetic drug in patients with type 2 diabetes mellitus with insufficient glycaemic control.
Interventions
DRUGMetformin
Metformin tablets 500-2250 mg a day (twice or three times per day)
DRUGBI 10773
BI 10773 low dose tablet once daily
Placebo tablets once daily
Placebo tablets 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
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* .Diagnosis of type 2 diabetes mellitus prior to informed consent * Male and female patients, on diet and exercise regimen, who are pre-treated with one of the following oral antidiabetic drugs: sulfonylurea, glinide, biguanide, Alpha-glucosidase inhibitor (a-GI), dipeptidyl peptidase-IV (DPP-IV) inhibitor or thiazolidinedione * glycosylated haemoglobin (HbA1c) at Visit 1: \>=7.0 to =\<10.0% (national glycohemoglobin standardization program)
Exclusion criteria
* Uncontrolled hyperglycaemia with a glucose level \>240 mg/dL (\>13.3 mmol/L) * Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 12 weeks prior to informed consent * Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Drug Related Adverse Events | After the first drug intake until 7 days after the last treatment administration, up to 383 days | Number of Patients With Drug Related Adverse Events after the first drug intake until 7 days after the last treatment administration, up to 383 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c | Baseline and 52 weeks | Change from baseline in HbA1c after 52 weeks of treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Hypoglycaemic Adverse Events | After the first drug intake until 7 days after the last treatment administration, up to 383 days | Number of patients with confirmed hypoglycaemic adverse events |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulfonylurea: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Sulfonylurea | 136 |
| Sulfonylurea: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Sulfonylurea | 137 |
| Sulfonylurea: Metformin 250mg tablet of metformin twice daily for 52 weeks, as an open-label treatment, for patients with background treatment of Sulfonylurea | 63 |
| Biguanide: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Biguanide | 68 |
| Biguanide: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Biguanide | 65 |
| Thiazolidinedione: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Thiazolidinedione | 137 |
| Thiazolidinedione: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Thiazolidinedione | 136 |
| Alpha Glucosidase Inhibitor: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Alpha glucosidase inhibitor | 69 |
| Alpha Glucosidase Inhibitor: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Alpha glucosidase inhibitor | 70 |
| DPP-IV Inhibitor: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of DPP-IV inhibitor | 68 |
| DPP-IV Inhibitor: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of DPP-IV inhibitor | 71 |
| Glinide: Empa 10mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Glinide | 70 |
| Glinide: Empa 25mg One tablet of empagliflozin (empa) once daily for 52 weeks as an add-on therapy for patients with a background treatment of Glinide | 70 |
| Total | 1,160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 3 | 2 | 2 | 5 | 6 | 2 | 3 | 5 | 6 | 1 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other reason not defined above | 2 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 1 | 1 | 0 | 3 | 4 | 2 | 5 | 4 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Sulfonylurea: Empa 25mg | Sulfonylurea: Metformin | Biguanide: Empa 10mg | Biguanide: Empa 25mg | Thiazolidinedione: Empa 10mg | Thiazolidinedione: Empa 25mg | Alpha Glucosidase Inhibitor: Empa 10mg | Alpha Glucosidase Inhibitor: Empa 25mg | DPP-IV Inhibitor: Empa 10mg | DPP-IV Inhibitor: Empa 25mg | Glinide: Empa 10mg | Sulfonylurea: Empa 10mg | Glinide: Empa 25mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 10.4 | 61.8 years STANDARD_DEVIATION 9.6 | 60.0 years STANDARD_DEVIATION 10.2 | 56.9 years STANDARD_DEVIATION 9.5 | 57.3 years STANDARD_DEVIATION 11.4 | 60.4 years STANDARD_DEVIATION 10.1 | 59.7 years STANDARD_DEVIATION 9.9 | 63.5 years STANDARD_DEVIATION 8.8 | 61.9 years STANDARD_DEVIATION 11.7 | 63.3 years STANDARD_DEVIATION 9.9 | 59.1 years STANDARD_DEVIATION 10.3 | 59.2 years STANDARD_DEVIATION 12.1 | 61.3 years STANDARD_DEVIATION 9.9 | 57.7 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 325 Participants | 41 Participants | 16 Participants | 30 Participants | 22 Participants | 23 Participants | 34 Participants | 18 Participants | 18 Participants | 27 Participants | 23 Participants | 23 Participants | 37 Participants | 13 Participants |
| Sex: Female, Male Male | 835 Participants | 96 Participants | 47 Participants | 38 Participants | 43 Participants | 114 Participants | 102 Participants | 51 Participants | 52 Participants | 41 Participants | 48 Participants | 47 Participants | 99 Participants | 57 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 73 / 136 | 74 / 137 | 44 / 63 | 32 / 68 | 35 / 65 | 77 / 137 | 74 / 136 | 40 / 69 | 34 / 70 | 37 / 68 | 36 / 71 | 30 / 70 | 38 / 70 |
| serious Total, serious adverse events | 10 / 136 | 7 / 137 | 3 / 63 | 7 / 68 | 2 / 65 | 12 / 137 | 12 / 136 | 2 / 69 | 5 / 70 | 7 / 68 | 5 / 71 | 1 / 70 | 4 / 70 |
Outcome results
Primary
Number of Patients With Drug Related Adverse Events
Number of Patients With Drug Related Adverse Events after the first drug intake until 7 days after the last treatment administration, up to 383 days
Time frame: After the first drug intake until 7 days after the last treatment administration, up to 383 days
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfonylurea: Empa 10mg | Number of Patients With Drug Related Adverse Events | 19 participants |
| Sulfonylurea: Empa 25mg | Number of Patients With Drug Related Adverse Events | 25 participants |
| Sulfonylurea: Metformin | Number of Patients With Drug Related Adverse Events | 13 participants |
| Biguanide: Empa 10mg | Number of Patients With Drug Related Adverse Events | 13 participants |
| Biguanide: Empa 25mg | Number of Patients With Drug Related Adverse Events | 9 participants |
| Thiazolidinedione: Empa 10mg | Number of Patients With Drug Related Adverse Events | 20 participants |
| Thiazolidinedione: Empa 25mg | Number of Patients With Drug Related Adverse Events | 19 participants |
| Alpha Glucosidase Inhibitor: Empa 10mg | Number of Patients With Drug Related Adverse Events | 7 participants |
| Alpha Glucosidase Inhibitor: Empa 25mg | Number of Patients With Drug Related Adverse Events | 5 participants |
| DPP-IV Inhibitor: Empa 10mg | Number of Patients With Drug Related Adverse Events | 9 participants |
| DPP-IV Inhibitor: Empa 25mg | Number of Patients With Drug Related Adverse Events | 18 participants |
| Glinide: Empa 10mg | Number of Patients With Drug Related Adverse Events | 9 participants |
| Glinide: Empa 25mg | Number of Patients With Drug Related Adverse Events | 9 participants |
Secondary
Change From Baseline in HbA1c
Change from baseline in HbA1c after 52 weeks of treatment
Time frame: Baseline and 52 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sulfonylurea: Empa 10mg | Change From Baseline in HbA1c | -0.93 percentage of HbA1c | Standard Error 0.05 |
| Sulfonylurea: Empa 25mg | Change From Baseline in HbA1c | -0.96 percentage of HbA1c | Standard Error 0.05 |
| Sulfonylurea: Metformin | Change From Baseline in HbA1c | -0.97 percentage of HbA1c | Standard Error 0.08 |
| Biguanide: Empa 10mg | Change From Baseline in HbA1c | -0.81 percentage of HbA1c | Standard Error 0.06 |
| Biguanide: Empa 25mg | Change From Baseline in HbA1c | -0.98 percentage of HbA1c | Standard Error 0.06 |
| Thiazolidinedione: Empa 10mg | Change From Baseline in HbA1c | -0.90 percentage of HbA1c | Standard Error 0.05 |
| Thiazolidinedione: Empa 25mg | Change From Baseline in HbA1c | -0.96 percentage of HbA1c | Standard Error 0.05 |
| Alpha Glucosidase Inhibitor: Empa 10mg | Change From Baseline in HbA1c | -0.87 percentage of HbA1c | Standard Error 0.06 |
| Alpha Glucosidase Inhibitor: Empa 25mg | Change From Baseline in HbA1c | -0.77 percentage of HbA1c | Standard Error 0.06 |
| DPP-IV Inhibitor: Empa 10mg | Change From Baseline in HbA1c | -1.00 percentage of HbA1c | Standard Error 0.06 |
| DPP-IV Inhibitor: Empa 25mg | Change From Baseline in HbA1c | -0.83 percentage of HbA1c | Standard Error 0.06 |
| Glinide: Empa 10mg | Change From Baseline in HbA1c | -0.98 percentage of HbA1c | Standard Error 0.08 |
| Glinide: Empa 25mg | Change From Baseline in HbA1c | -0.98 percentage of HbA1c | Standard Error 0.08 |
Other Pre-specified
Confirmed Hypoglycaemic Adverse Events
Number of patients with confirmed hypoglycaemic adverse events
Time frame: After the first drug intake until 7 days after the last treatment administration, up to 383 days
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfonylurea: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 6 participants |
| Sulfonylurea: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 9 participants |
| Sulfonylurea: Metformin | Confirmed Hypoglycaemic Adverse Events | 5 participants |
| Biguanide: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Biguanide: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 1 participants |
| Thiazolidinedione: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 2 participants |
| Thiazolidinedione: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 1 participants |
| Alpha Glucosidase Inhibitor: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Alpha Glucosidase Inhibitor: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| DPP-IV Inhibitor: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| DPP-IV Inhibitor: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 1 participants |
| Glinide: Empa 10mg | Confirmed Hypoglycaemic Adverse Events | 0 participants |
| Glinide: Empa 25mg | Confirmed Hypoglycaemic Adverse Events | 2 participants |