Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia, Europe, Oceania and South America. The aim of this clinical trial is to generate data demonstrating how to intensify diabetes treatment using BIAsp 30 (biphasic insulin aspart 30) by adding or substituting BIAsp 30 to sitagliptin in various regimens for type 2 patients inadequately controlled on sitagliptin and metformin (with or without other oral anti-diabetic drugs (OADs)). The trial is conducted as a phase 4 trial in the majority of the participating countries. However, in some countries the trial is conducted as phase 3b.
Interventions
DRUGbiphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) twice daily. Individually adjusted dose.
DRUGsitagliptin
Subjects will continue on their pre-trial sitagliptin treatment.
DRUGmetformin
Subjects will continue on their pre-trial metformin treatment.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes for a minimum of 6 months prior to screening (Visit 1) * Stable treatment with a total daily dose of at least 1000 mg of metformin (with or without additional oral anti-diabetic drugs (OADs) treatment). The metformin dose must have been unchanged for at least 3 months prior to screening (Visit 1) * Stable treatment with a total daily dose of at least 100 mg sitagliptin. The sitagliptin dose must have been unchanged for at least 3 months prior to screening (Visit 1) * Subject is insulin-naïve (never previously treated with insulin). (However, short term insulin use due to intermittent illness of up to 14 days or insulin treatment for gestational diabetes is allowed) * HbA1c (glycosylated haemoglobin) between 7.0 to 10.0 % (53-86 mmol/mol) (both inclusive) by central laboratory analysis demonstrating inadequate control on sitagliptin and metformin (with or without other OADs) * Body Mass Index (BMI) below or equal to 40.0 kg/m\^2 * Able and willing to eat at least 2 meals (breakfast and dinner) every day during the trial
Exclusion criteria
* Treatment with thiazolidinedione (TZD) or glucagon-like-peptide-1 (GLP-1) receptor agonist within the last 3 months prior to screening (Visit 1) * Cardiac disease within the last 6 months prior to screening (Visit 1), defined as: decompensated heart failure New York Heart Association (NYHA) class III or IV; unstable angina pectoris; or myocardial infarction * Severe hypertension, systolic blood pressure equal to or above 180 mm Hg or diastolic blood pressure equal to or above 100 mm Hg, after 5 minutes rest in the sitting position using mean value of 3 measurements at screening (Visit 1) * Anticipated change of dose of any systemic treatment with products, which in the trial physician's opinion could interfere with glucose metabolism (e.g., systemic corticosteroids) * Clinically significant diseases (except for conditions associated with type 2 diabetes) which, in the trial physician's opinion may confound the results of the trial or pose additional risk in administering trial product(s) * Impaired hepatic function as indicated by aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) above 2.5 times the upper normal range, according to central laboratory reference ranges * Impaired renal function as indicated by serum creatinine levels equal to or above 133 micromol/L (1.5 mg/dL) for males and equal to or above 124 micromol/L (1.4 mg/dL) for females or estimated creatinine clearance below 60 mL/min, based on the Cockroft & Gault formula and according to local practise for metformin use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) | Week 0 to Week 24 | Estimated mean change from baseline in HbA1c after 24 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%) | After 24 weeks of treatment | Proportion of subjects achieving HbA1c equal to or below 6.5% after 24 weeks of treatment. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Week 0 to Week 24 | Estimated mean change from baseline in fasting plasma glucose (FPG) |
| Prandial Plasma Glucose (PPG) Increments at Breakfast | After 24 weeks of treatment | Estimated mean post prandial increments at breakfast after 24 weeks of treatment. |
| Prandial Plasma Glucose (PPG) Increments at Lunch. | After 24 weeks of treatment | Estimated mean post prandial increments at lunch after 24 weeks of treatment. |
| Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%) | After 24 weeks of treatment | Proportion of subjects achieving HbA1c below 7.0% after 24 weeks of treatment |
| Prandial Plasma Glucose (PPG) Overall Mean Increment. | After 24 weeks of treatment | Estimated overall mean post prandial increment after 24 weeks of treatment. |
| Adverse Events (AEs) | Week 0 to Week 24 | Rate of AEs per 100 years of patient exposure. An adverse event was defined as treatment emergent if the event had onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. |
| Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Week 0 to Week 24 | Number of treatment emergent hypoglycaemic episodes. Treatment emergent hypoglycaemic episode: if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. Nocturnal: Time of onset between 00:01 and 05:59 a.m. (both included). Additional minor hypoglycaemic episode: symptomatic or asymptomatic hypoglycaemia with blood glucose (BG) values \< 2.8 mmol/L (50 mg/dL) or plasma glucose (PG) \< 3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself. |
| Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes. | Week 0 to Week 24 | Estimated mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) 'total score' to end of trial. The score measured treatment satisfaction. The scores were transformed to a 0-100 scale with higher scores indicating greater satisfaction. |
| Prandial Plasma Glucose (PPG) Increments at Dinner. | After 24 weeks of treatment | Estimated mean post prandial increments at dinner after 24 weeks of treatment. |
Countries
Argentina, Australia, Brazil, Greece, India, Malaysia, Portugal, South Korea, Thailand, Turkey (Türkiye)
Participant flow
Recruitment details
The trial was conducted at 60 sites in 10 countries as follows: Argentina (6); Australia (2); Brazil (4); Greece (5); India (17); Malaysia (3); Portugal (6); Republic of Korea (7); Thailand (5); Turkey (5)
Pre-assignment details
Subjects on pre-trial metformin (1000 mg/day) (± additional OAD treatment) continued their medication. Subjects on pre-trial sitagliptin (100 mg/day) either continued or discontinued their sitagliptin treatment depending on the treatment group the subjects were randomised to.
Participants by arm
| Arm | Count |
|---|---|
| BID + Met Biphasic insulin aspart 30 (BIAsp 30) was injected twice daily, 6 U before breakfast and 6 U before dinner (evening meal), subcutaneously (under the skin) for 24 weeks. Dosing of BIAsp 30 was adjusted individually according to the titration guideline and the subject's self-measured plasma glucose (SMPG) levels. Subjects continued on their pre-trial metformin (1000 mg/day) treatment. | 194 |
| BID + Sita + Met Biphasic insulin aspart 30 (BIAsp 30) was injected twice daily, 6 U before breakfast and 6 U before dinner (evening meal), subcutaneously (under the skin) for 24 weeks. Dosing of BIAsp 30 was adjusted individually according to the titration guideline and the subject's self-measured plasma glucose (SMPG) levels. Subjects continued on their pre-trial metformin (1000 mg/day) and sitagliptin (100 mg/day) treatments. | 195 |
| OD + Sita + Met Biphasic insulin aspart 30 (BIAsp 30) was injected once daily, 12 U before dinner (evening meal), subcutaneously (under the skin) for 24 weeks. Dosing of BIAsp 30 was adjusted individually according to the titration guideline and the subject's self-measured plasma glucose (SMPG) levels. Subjects continued on their pre-trial metformin (1000 mg/day) and sitagliptin (100 mg/day) treatments. | 193 |
| Total | 582 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 3 | 1 |
| Overall Study | Unsclassified | 10 | 4 | 3 |
| Overall Study | Withdrawal Criteria | 7 | 2 | 7 |
Baseline characteristics
| Characteristic | BID + Met | BID + Sita + Met | OD + Sita + Met | Total |
|---|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 9.5 | 56.3 years STANDARD_DEVIATION 10.2 | 55.7 years STANDARD_DEVIATION 10.4 | 55.6 years STANDARD_DEVIATION 10 |
| Body Mass Index (BMI) | 29.3 kg/m^2 STANDARD_DEVIATION 4.3 | 29.4 kg/m^2 STANDARD_DEVIATION 4.5 | 29.4 kg/m^2 STANDARD_DEVIATION 5 | 29.4 kg/m^2 STANDARD_DEVIATION 4.6 |
| Body Weight | 79.4 kg STANDARD_DEVIATION 15.8 | 78.3 kg STANDARD_DEVIATION 16.1 | 77.5 kg STANDARD_DEVIATION 16.8 | 78.4 kg STANDARD_DEVIATION 16.2 |
| Fasting plasma glucose (FPG) | 8.9 mmol/L STANDARD_DEVIATION 2.2 | 9.3 mmol/L STANDARD_DEVIATION 2.8 | 8.7 mmol/L STANDARD_DEVIATION 2.7 | 9.0 mmol/L STANDARD_DEVIATION 2.6 |
| Gender Female | 83 Participants | 101 Participants | 97 Participants | 281 Participants |
| Gender Male | 111 Participants | 94 Participants | 96 Participants | 301 Participants |
| Glycosylated haemoglobin (HbA1c) | 8.4 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.4 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.4 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.4 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
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 | 30 / 192 | 25 / 193 | 32 / 190 |
| serious Total, serious adverse events | 7 / 192 | 5 / 193 | 4 / 190 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Estimated mean change from baseline in HbA1c after 24 weeks of treatment.
Time frame: Week 0 to Week 24
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 559 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -1.27 percentage of glycosylated haemoglobin | Standard Error 0.07 |
| BID + Sita + Met | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -1.51 percentage of glycosylated haemoglobin | Standard Error 0.07 |
| OD + Sita + Met | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -1.15 percentage of glycosylated haemoglobin | Standard Error 0.07 |
Comparison: The null-hypothesis (H0) was tested against the alternative hypothesis (HA) in each of the comparisons as given by:~H0: D = 0% against HA: D ≠ 0% D being the mean treatment difference for change from baseline in HbA1c after 24 weeks of treatment between the two treatment group comparisons (BID+Met and BID+Sita+Met).p-value: 0.01195% CI: [0.06, 0.43]Regression, Linear
Comparison: The null-hypothesis (H0) was tested against the alternative hypothesis (HA) in each of the comparisons as given by: H0: D = 0% against HA: D ≠ 0% D being the mean treatment difference for change from baseline in HbA1c after 24 weeks of treatment between the two treatment group comparisons (BID+Sita+Met and OD+Sita+Met).p-value: 0.23195% CI: [-0.3, 0.07]Regression, Linear
Comparison: The null-hypothesis (H0) was tested against the alternative hypothesis (HA) in each of the comparisons as given by: H0: D = 0% against HA: D ≠ 0% D being the mean treatment difference for change from baseline in HbA1c after 24 weeks of treatment between the two treatment group comparisons (BID+Sita+Met and OD+Sita+Met).p-value: <0.00195% CI: [-0.54, -0.17]Regression, Linear
Secondary
Adverse Events (AEs)
Rate of AEs per 100 years of patient exposure. An adverse event was defined as treatment emergent if the event had onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.
Time frame: Week 0 to Week 24
Population: Safety analysis set included all subjects receiving at least one dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BID + Met | Adverse Events (AEs) | Mild adverse events | 185.2 Events/100 years of patient exposure |
| BID + Met | Adverse Events (AEs) | Fatal adverse events | 0 Events/100 years of patient exposure |
| BID + Met | Adverse Events (AEs) | Severe adverse events | 6.0 Events/100 years of patient exposure |
| BID + Met | Adverse Events (AEs) | All treatment emergent adverse events | 262.2 Events/100 years of patient exposure |
| BID + Met | Adverse Events (AEs) | Moderate adverse events | 71.0 Events/100 years of patient exposure |
| BID + Met | Adverse Events (AEs) | Serious adverse events | 8.4 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | All treatment emergent adverse events | 209.9 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | Mild adverse events | 124.8 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | Serious adverse events | 5.8 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | Severe adverse events | 10.5 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | Fatal adverse events | 0 Events/100 years of patient exposure |
| BID + Sita + Met | Adverse Events (AEs) | Moderate adverse events | 74.6 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | Fatal adverse events | 0 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | All treatment emergent adverse events | 281.2 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | Serious adverse events | 10.5 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | Severe adverse events | 7.0 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | Moderate adverse events | 79.7 Events/100 years of patient exposure |
| OD + Sita + Met | Adverse Events (AEs) | Mild adverse events | 194.5 Events/100 years of patient exposure |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Estimated mean change from baseline in fasting plasma glucose (FPG)
Time frame: Week 0 to Week 24
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 556 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.90 mmol/L | Standard Error 0.14 |
| BID + Sita + Met | Change From Baseline in Fasting Plasma Glucose (FPG) | -2.03 mmol/L | Standard Error 0.14 |
| OD + Sita + Met | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.96 mmol/L | Standard Error 0.14 |
p-value: 0.5295% CI: [-0.26, 0.52]Regression, Linear
p-value: 0.78895% CI: [-0.34, 0.45]Regression, Linear
p-value: 0.70895% CI: [-0.46, 0.31]Regression, Linear
Secondary
Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes.
Estimated mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) 'total score' to end of trial. The score measured treatment satisfaction. The scores were transformed to a 0-100 scale with higher scores indicating greater satisfaction.
Time frame: Week 0 to Week 24
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 545 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes. | 6.22 scores | Standard Error 0.82 |
| BID + Sita + Met | Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes. | 5.93 scores | Standard Error 0.81 |
| OD + Sita + Met | Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes. | 6.20 scores | Standard Error 0.81 |
p-value: 0.895% CI: [-1.97, 2.56]Regression, Linear
p-value: 0.98995% CI: [-2.26, 2.29]Regression, Linear
p-value: 0.80995% CI: [-2.52, 1.97]Regression, Linear
Secondary
Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes.
Number of treatment emergent hypoglycaemic episodes. Treatment emergent hypoglycaemic episode: if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. Nocturnal: Time of onset between 00:01 and 05:59 a.m. (both included). Additional minor hypoglycaemic episode: symptomatic or asymptomatic hypoglycaemia with blood glucose (BG) values \< 2.8 mmol/L (50 mg/dL) or plasma glucose (PG) \< 3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself.
Time frame: Week 0 to Week 24
Population: Safety analysis set included all subjects receiving at least one dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BID + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (ADA) | 515 episodes |
| BID + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (ADA) | 68 episodes |
| BID + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (additional minor) | 163 episodes |
| BID + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (additional minor) | 21 episodes |
| BID + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (additional minor) | 14 episodes |
| BID + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (ADA) | 440 episodes |
| BID + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (additional minor) | 112 episodes |
| BID + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (ADA) | 54 episodes |
| OD + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (additional minor) | 23 episodes |
| OD + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Nocturnal (ADA) | 63 episodes |
| OD + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (additional minor) | 71 episodes |
| OD + Sita + Met | Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes. | Diurnal (ADA) | 249 episodes |
Secondary
Prandial Plasma Glucose (PPG) Increments at Breakfast
Estimated mean post prandial increments at breakfast after 24 weeks of treatment.
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 555 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Prandial Plasma Glucose (PPG) Increments at Breakfast | 2.01 mmol/L | Standard Error 0.19 |
| BID + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Breakfast | 1.73 mmol/L | Standard Error 0.19 |
| OD + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Breakfast | 2.89 mmol/L | Standard Error 0.19 |
p-value: 0.29195% CI: [-0.24, 0.81]Regression, Linear
p-value: 0.00195% CI: [-1.41, -0.35]Regression, Linear
p-value: <0.00195% CI: [-1.69, -0.64]Regression, Linear
Secondary
Prandial Plasma Glucose (PPG) Increments at Dinner.
Estimated mean post prandial increments at dinner after 24 weeks of treatment.
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 550 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Prandial Plasma Glucose (PPG) Increments at Dinner. | 0.89 mmol/L | Standard Error 0.21 |
| BID + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Dinner. | 1.01 mmol/L | Standard Error 0.2 |
| OD + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Dinner. | 0.17 mmol/L | Standard Error 0.21 |
p-value: 0.67495% CI: [-0.7, 0.45]Regression, Linear
p-value: 0.01595% CI: [0.14, 1.3]Regression, Linear
p-value: 0.00495% CI: [0.27, 1.41]Regression, Linear
Secondary
Prandial Plasma Glucose (PPG) Increments at Lunch.
Estimated mean post prandial increments at lunch after 24 weeks of treatment.
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 548 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Prandial Plasma Glucose (PPG) Increments at Lunch. | 3.05 mmol/L | Standard Error 0.22 |
| BID + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Lunch. | 2.19 mmol/L | Standard Error 0.21 |
| OD + Sita + Met | Prandial Plasma Glucose (PPG) Increments at Lunch. | 2.52 mmol/L | Standard Error 0.21 |
p-value: 0.00595% CI: [0.26, 1.45]Regression, Linear
p-value: 0.08595% CI: [-0.07, 1.12]Regression, Linear
p-value: 0.27595% CI: [-0.92, 0.26]Regression, Linear
Secondary
Prandial Plasma Glucose (PPG) Overall Mean Increment.
Estimated overall mean post prandial increment after 24 weeks of treatment.
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 557 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BID + Met | Prandial Plasma Glucose (PPG) Overall Mean Increment. | 1.97 mmol/L | Standard Error 0.12 |
| BID + Sita + Met | Prandial Plasma Glucose (PPG) Overall Mean Increment. | 1.66 mmol/L | Standard Error 0.12 |
| OD + Sita + Met | Prandial Plasma Glucose (PPG) Overall Mean Increment. | 1.88 mmol/L | Standard Error 0.12 |
p-value: 0.0895% CI: [-0.04, 0.65]Regression, Linear
p-value: 0.61395% CI: [-0.26, 0.43]Regression, Linear
p-value: 0.21395% CI: [-0.56, 0.13]Regression, Linear
Secondary
Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%)
Proportion of subjects achieving HbA1c equal to or below 6.5% after 24 weeks of treatment.
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 559 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BID + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%) | 30.6 percentage (%) of subjects |
| BID + Sita + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%) | 40.7 percentage (%) of subjects |
| OD + Sita + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%) | 25.1 percentage (%) of subjects |
p-value: 0.0295% CI: [0.38, 0.92]Regression, Logistic
p-value: 0.28695% CI: [0.81, 2.07]Regression, Logistic
p-value: <0.00195% CI: [1.39, 3.47]Regression, Logistic
Secondary
Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%)
Proportion of subjects achieving HbA1c below 7.0% after 24 weeks of treatment
Time frame: After 24 weeks of treatment
Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 559 subjects contributed to the statistical analysis at Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BID + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%) | 49.7 percentage (%) of subjects |
| BID + Sita + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%) | 59.8 percentage (%) of subjects |
| OD + Sita + Met | Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%) | 46.5 percentage (%) of subjects |
p-value: 0.02295% CI: [0.39, 0.93]Regression, Logistic
p-value: 0.61895% CI: [0.73, 1.71]Regression, Logistic
p-value: 0.00595% CI: [1.2, 2.85]Regression, Logistic