Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Vildagliptin, Elderly Patients
Brief summary
The purpose of this study was to determine whether the initiation of a vildagliptin plus metformin combination regimen would result in more durable glycemic control than metformin monotherapy in treatment-naïve patients with type-2 diabetes mellitus (T2DM).
Detailed description
This was a multi-center, double-blind, placebo-controlled, 2-arm, parallel group study with a run-in period and up to 5 years treatment period. Following a screening visit (Visit 1) and a screening period of up to 2 weeks, treatment-naïve patients, meeting all eligibility criteria entered the run-in period at Visit 2. * Run-in period: At Visit 2, in all eligible patients, metformin treatment was initiated and/or up-titrated. At the end of the 3-week run-in period, patients who were able to tolerate a total dose of at least 1000 mg and up to 2000 mg daily proceeded to randomization and started in Period 1. * Period 1 (vildagliptin/metformin combination versus metformin): At Visit 3, patients were randomized 1:1 to one of the following study regimens: * Metformin up to 1000 mg bid plus vildagliptin 50mg bid or * Metformin up to 1000 mg bid plus matching placebo bid The duration of Period 1 could differ between patients depending on the time when the second of two HbA1c measurements taken at two consecutive visits after randomisation confirmed HbA1c ≥ 7.0%. • Period 2 (vildagliptin/metformin combination versus vildagliptin add-on to metformin): In the case of two consecutive HbA1c measurements ≥7.0% from two consecutive study visits during Period 1, patients who were randomised to the placebo arm in Period 1 received vildagliptin 50 mg bid. Patients who were randomised to the active vildagliptin 50 mg bid arm in Period 1 continued to receive vildagliptin 50 mg bid. All patients continued to take their metformin dose unchanged. Period 2 remained masked to the patient and both patients and investigators remained masked to the treatment allocation in Period 1. If, during Period 2, therapy intensification was required in accordance with the local guidelines, the patient entered Period 3. The duration of Period 2 could differ between patients. End of Period 2 was considered when insulin treatment was initiated, or alternatively when the patient was discontinued because insulin treatment was not initiated in Period 3. • Period 3 (insulin initiation): In Period 3, patients were to be initiated on open-label insulin. The study drug regimen continued unchanged and remained masked to the patient in Period 3 and both patients and investigators remained masked to the treatment allocation in Period 1.
Interventions
DRUGvildagliptin
One tablet (50 mg oral) of vildagliptin in the morning and one tablet in the evening with or without food.
DRUGMetformin
Twice daily (bid) regimen during or after meals at the same time as vildagliptin.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Type 2 Diabetes Mellitus (T2DM) diagnosed ≤ 24 months ago * glycosylated hemoglobin (HbA1c) ≥6.5% and ≤7.5% at Visit 1 * Treatment-naïve. * Body mass index (BMI) ≥22 and ≤40 kg/m2 at Visit 1 Key
Exclusion criteria
* Pregnant or nursing (lactating) women * Fasting plasma glucose (FPG) ≥ 270 mg/dL (≥ 15.0 mmol/L) * Previous or current participation in any vildagliptin clinical study. * History of hypersensitivity to dipeptidyl peptidase-4 (DPP-4) inhibitors. * Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. * Donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks of start of study or a blood transfusion within the past 12 weeks or planned regular transfusions during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Initial Treatment Failure | Visit 4 (Week 13) up to End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) | Treatment failure was defined as two consecutive scheduled visits with HbA1c \>= 7.0% (starting from 13 weeks after randomization) and the time to treatment failure was the number of days from randomization to the second of the consecutive scheduled visits. Participants who discontinued the study for any reason during Period 1 were censored at the date of discontinuation. Participants who remained under the threshold (or whose measurement above the threshold was not confirmed at next scheduled visit) were censored at the date of last study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2 | From 26 weeks after start of Period 2 to end of Period 2 | The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years). HbA1c data collected from 26 weeks after the start of Period 2 to the end of Period 2 were included in the analysis, for participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis. |
| Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1 | Visit 5 (Week 26) to End of Period 1 | Rate of loss in glycemic control was estimated using the slope of FPG over time (years). FPG (fasting plasma glucose) data from Week 26 to the end of Period 1 was included in the analysis. Baseline FPG was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement is missing. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis. |
| Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2 | From 26 weeks after start of Period 2 to end of Period 2 | Rate of loss in glycemic control was estimated using the slope of FPG over time (years). FPG (fasting plasma glucose) data from 26 weeks after the start of Period 2 to then end of Period 2 was included in the analysis. Only participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3 were included. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis. |
| Rate of Loss in Glycemic Control During Period 1 | Visit 5 (Week 26) to End of Period 1 | The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years). HbA1c data collected from Week 26 up to and including the end of Period 1 visit was included in the analysis. Baseline HbA1c was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement was missing. End of Period 1 was defined as the final post-baseline assessment obtained at any visit within Period 1 (scheduled or unscheduled), up to the last scheduled visit. |
| Rate of Change in Insulin Sensitivity From Baseline to End of Study | Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) | The rate of change of insulin sensitivity is assessed using the slope of OGIS over time (years) where Oral glucose insulin sensitivity (OGIS) was calculated as a function of glucose and insulin, using meal-test data from 0 to 120 minutes. Baseline OGIS is derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements are missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively. |
| Percentage of Participants With Adverse Events, Serious Adverse Events and Death | From first dose of study treatment until End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) | Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that LAF237 is safe for the treatment of naïve patients with type 2 diabetes mellitus through the monitoring of relevant clinical and laboratory safety parameters. |
| Rate of Loss of Beta Cell Function From Baseline to End of Study | Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation) | The rate of change of beta cell function was assessed using the slope of AUC of ISR/G over time (years) where AUC of ISR/G is defined as (Area under curve of Insulin secretion rate (derived using c-peptide))/(Area under curve of Glucose), using meal-test data from 0 to 120 minutes. Baseline AUC of ISR/G was derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements were missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Colombia, Czechia, Dominican Republic, Estonia, Finland, Germany, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Norway, Panama, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye)
Participant flow
Recruitment details
It was planned to screen approximately 4000 patients in order to randomize 2000 patients. Actually, 2001 patients were randomized, 998 patients into the Vilda 50mg bid + metformin group and 1003 into the placebo + metformin group.
Participants by arm
| Arm | Count |
|---|---|
| Vilda 50mg Bid + Metformin vildagliptin (Vilda 50mg bid) + Metformin | 998 |
| Placebo + Metformin Placebo of vildagliptin (Vilda 50mg bid) + Metformin | 1,003 |
| Total | 2,001 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 3 | 7 |
| Overall Study | Abnormal test procedure result(s) | 1 | 0 |
| Overall Study | Administrative problems | 96 | 94 |
| Overall Study | Adverse Event | 28 | 44 |
| Overall Study | Death | 13 | 9 |
| Overall Study | Lost to Follow-up | 17 | 24 |
| Overall Study | New therapy for study indication | 8 | 6 |
| Overall Study | No longer requires study drug | 1 | 1 |
| Overall Study | Protocol deviation | 9 | 19 |
| Overall Study | Unsatisfactory therapeutic effect | 6 | 8 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Vilda 50mg Bid + Metformin | Placebo + Metformin | Total |
|---|---|---|---|
| Age, Continuous | 54.1 Years STANDARD_DEVIATION 9.54 | 54.6 Years STANDARD_DEVIATION 9.24 | 54.3 Years STANDARD_DEVIATION 9.39 |
| Duration of type 2 diabetes | 6.2 months STANDARD_DEVIATION 7 | 6.6 months STANDARD_DEVIATION 8.05 | 6.4 months STANDARD_DEVIATION 7.55 |
| fasting plasma glucose (FPG) | 7.1 mmol/l STANDARD_DEVIATION 1.4 | 7.2 mmol/l STANDARD_DEVIATION 1.47 | 7.1 mmol/l STANDARD_DEVIATION 1.44 |
| Glomerular Filtration Rate (Modification of Diet in Renal Disease) Mild (>=50 - <=80) | 333 Participants | 337 Participants | 670 Participants |
| Glomerular Filtration Rate (Modification of Diet in Renal Disease) Missing | 2 Participants | 0 Participants | 2 Participants |
| Glomerular Filtration Rate (Modification of Diet in Renal Disease) Moderate (>=30 - <50) | 3 Participants | 4 Participants | 7 Participants |
| Glomerular Filtration Rate (Modification of Diet in Renal Disease) Normal (>80) | 660 Participants | 661 Participants | 1321 Participants |
| Glomerular Filtration Rate (Modification of Diet in Renal Disease) Severe (<30) | 0 Participants | 1 Participants | 1 Participants |
| glycosylated hemoglobin (HbA1c) | 6.7 Percent STANDARD_DEVIATION 0.45 | 6.7 Percent STANDARD_DEVIATION 0.47 | 6.7 Percent STANDARD_DEVIATION 0.46 |
| Is subject a current smoker? Is subject a current smoker?=No | 844 Participants | 867 Participants | 1711 Participants |
| Is subject a current smoker? Is subject a current smoker?=Yes | 154 Participants | 136 Participants | 290 Participants |
| Race/Ethnicity, Customized Asian | 186 Participants | 187 Participants | 373 Participants |
| Race/Ethnicity, Customized Black | 26 Participants | 23 Participants | 49 Participants |
| Race/Ethnicity, Customized Caucasian | 605 Participants | 612 Participants | 1217 Participants |
| Race/Ethnicity, Customized Native American | 103 Participants | 107 Participants | 210 Participants |
| Race/Ethnicity, Customized Other | 78 Participants | 74 Participants | 152 Participants |
| Sex: Female, Male Female | 545 Participants | 515 Participants | 1060 Participants |
| Sex: Female, Male Male | 453 Participants | 488 Participants | 941 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 998 | 9 / 1,001 | 22 / 1,999 |
| other Total, other adverse events | 582 / 998 | 566 / 1,001 | 1,148 / 1,999 |
| serious Total, serious adverse events | 166 / 998 | 183 / 1,001 | 349 / 1,999 |
Outcome results
Primary
Time to Initial Treatment Failure
Treatment failure was defined as two consecutive scheduled visits with HbA1c \>= 7.0% (starting from 13 weeks after randomization) and the time to treatment failure was the number of days from randomization to the second of the consecutive scheduled visits. Participants who discontinued the study for any reason during Period 1 were censored at the date of discontinuation. Participants who remained under the threshold (or whose measurement above the threshold was not confirmed at next scheduled visit) were censored at the date of last study visit.
Time frame: Visit 4 (Week 13) up to End of Study (Study Drug Discontinuation or Premature Subject Discontinuation)
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | Year 3 | 31.24 Rate (%) |
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | Year 5 | 46.41 Rate (%) |
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | Year 2 | 17.79 Rate (%) |
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | > Year 5 | 52.67 Rate (%) |
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | Year 4 | 39.84 Rate (%) |
| Vilda 50mg Bid + Metformin | Time to Initial Treatment Failure | Weeks 13-52 | 7.81 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | Year 2 | 34.67 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | Weeks 13-52 | 19.97 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | Year 3 | 48.31 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | Year 4 | 59.29 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | Year 5 | 66.57 Rate (%) |
| Placebo + Metformin | Time to Initial Treatment Failure | > Year 5 | 74.39 Rate (%) |
p-value: <0.00195% CI: [0.45, 0.58]Regression, Cox
Secondary
Percentage of Participants With Adverse Events, Serious Adverse Events and Death
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that LAF237 is safe for the treatment of naïve patients with type 2 diabetes mellitus through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From first dose of study treatment until End of Study (Study Drug Discontinuation or Premature Subject Discontinuation)
Population: Safety Set (SAF). Percentages are based on the number of patients starting each period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Adverse Event (AEs) | 83.5 Percentage of Participants |
| Vilda 50mg Bid + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Serious Adverse Event (SAEs) | 16.6 Percentage of Participants |
| Vilda 50mg Bid + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Deaths | 1.3 Percentage of Participants |
| Placebo + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Adverse Event (AEs) | 83.2 Percentage of Participants |
| Placebo + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Serious Adverse Event (SAEs) | 18.3 Percentage of Participants |
| Placebo + Metformin | Percentage of Participants With Adverse Events, Serious Adverse Events and Death | On-treatment Deaths | 0.9 Percentage of Participants |
Secondary
Rate of Change in Insulin Sensitivity From Baseline to End of Study
The rate of change of insulin sensitivity is assessed using the slope of OGIS over time (years) where Oral glucose insulin sensitivity (OGIS) was calculated as a function of glucose and insulin, using meal-test data from 0 to 120 minutes. Baseline OGIS is derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements are missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively.
Time frame: Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation)
Population: Full Analysis Set (FAS) meal-test subset
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of Period 1 | -4.61 Rate (%) | Standard Error 1.38 |
| Vilda 50mg Bid + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of Period 2 | -6.07 Rate (%) | Standard Error 1.2 |
| Vilda 50mg Bid + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of study | -6.39 Rate (%) | Standard Error 1.15 |
| Placebo + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of Period 1 | 0.41 Rate (%) | Standard Error 1.66 |
| Placebo + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of Period 2 | -0.99 Rate (%) | Standard Error 1.24 |
| Placebo + Metformin | Rate of Change in Insulin Sensitivity From Baseline to End of Study | From Week 13 to end of study | -1.01 Rate (%) | Standard Error 1.17 |
Comparison: From Week 13 to end of Period 1p-value: 0.0295% CI: [-9.26, -0.79]Mixed Models Analysis
Comparison: From Week 13 to end of Period 2p-value: 0.00395% CI: [-8.46, -1.69]Mixed Models Analysis
Comparison: From Week 13 to end of studyp-value: 0.00195% CI: [-8.61, -2.16]Mixed Models Analysis
Secondary
Rate of Loss in Glycemic Control During Period 1
The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years). HbA1c data collected from Week 26 up to and including the end of Period 1 visit was included in the analysis. Baseline HbA1c was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement was missing. End of Period 1 was defined as the final post-baseline assessment obtained at any visit within Period 1 (scheduled or unscheduled), up to the last scheduled visit.
Time frame: Visit 5 (Week 26) to End of Period 1
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Loss in Glycemic Control During Period 1 | 0.24 Rate (%) | Standard Error 0.01 |
| Placebo + Metformin | Rate of Loss in Glycemic Control During Period 1 | 0.27 Rate (%) | Standard Error 0.01 |
p-value: 0.04295% CI: [-0.05, 0]Mixed Models Analysis
Secondary
Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1
Rate of loss in glycemic control was estimated using the slope of FPG over time (years). FPG (fasting plasma glucose) data from Week 26 to the end of Period 1 was included in the analysis. Baseline FPG was the sample obtained on day 1, or the sample obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurement is missing. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
Time frame: Visit 5 (Week 26) to End of Period 1
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1 | 0.25 Rate (%) | Standard Error 0.01 |
| Placebo + Metformin | Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1 | 0.26 Rate (%) | Standard Error 0.01 |
p-value: 0.5395% CI: [-0.05, 0.02]Mixed Models Analysis
Secondary
Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2
Rate of loss in glycemic control was estimated using the slope of FPG over time (years). FPG (fasting plasma glucose) data from 26 weeks after the start of Period 2 to then end of Period 2 was included in the analysis. Only participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3 were included. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
Time frame: From 26 weeks after start of Period 2 to end of Period 2
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2 | 1.27 Rate (%) | Standard Error 0.25 |
| Placebo + Metformin | Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2 | 0.99 Rate (%) | Standard Error 0.19 |
p-value: 0.38195% CI: [-0.35, 0.9]Mixed Models Analysis
Secondary
Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2
The rate of loss in glycemic control was estimated using the slope of HbA1c over time (years). HbA1c data collected from 26 weeks after the start of Period 2 to the end of Period 2 were included in the analysis, for participants who started insulin therapy in Period 3 or discontinued during Period 2 due to being unable or unwilling to initiate insulin therapy in period 3. Participants who completed the study in Period 1 or Period 2 were not be included in the analysis.
Time frame: From 26 weeks after start of Period 2 to end of Period 2
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2 | 1.11 Rate (%) | Standard Error 0.15 |
| Placebo + Metformin | Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2 | 1.02 Rate (%) | Standard Error 0.12 |
p-value: 0.63595% CI: [-0.29, 0.47]Mixed Models Analysis
Secondary
Rate of Loss of Beta Cell Function From Baseline to End of Study
The rate of change of beta cell function was assessed using the slope of AUC of ISR/G over time (years) where AUC of ISR/G is defined as (Area under curve of Insulin secretion rate (derived using c-peptide))/(Area under curve of Glucose), using meal-test data from 0 to 120 minutes. Baseline AUC of ISR/G was derived based on samples obtained on day 1, or samples obtained at an earlier visit (scheduled or unscheduled) which was closest to Day 1, if the Day 1 measurements were missing. Three analyses were included, using data from Week 13 to the end of Period 1, end of Period 2 and end of study, respectively.
Time frame: Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation)
Population: Full Analysis Set (FAS) meal-test subset
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilda 50mg Bid + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of Period 1 | -0.60 Rate (%) | Standard Error 0.15 |
| Vilda 50mg Bid + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of Period 2 | -0.93 Rate (%) | Standard Error 0.14 |
| Vilda 50mg Bid + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of study | -1.04 Rate (%) | Standard Error 0.15 |
| Placebo + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of Period 1 | -0.53 Rate (%) | Standard Error 0.18 |
| Placebo + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of Period 2 | -0.43 Rate (%) | Standard Error 0.15 |
| Placebo + Metformin | Rate of Loss of Beta Cell Function From Baseline to End of Study | From Week 13 to end of study | -0.46 Rate (%) | Standard Error 0.15 |
Comparison: From Week 13 to end of Period 1p-value: 0.74495% CI: [-0.53, 0.38]Mixed Models Analysis
Comparison: From Week 13 to end of Period 2p-value: 0.01795% CI: [-0.91, -0.09]Mixed Models Analysis
Comparison: From Week 13 to end of studyp-value: 0.00695% CI: [-0.99, -0.17]Mixed Models Analysis