Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes mellitus, type 2, nateglinide, acarbose, hyperglycemia, dyslipidemias, C-reactive protein
Brief summary
This study was conducted to demonstrate superiority of nateglinide in postprandial glucose fluctuation, dyslipidemia, and inflammatory status improvement.
Interventions
DRUGNateglinide 120 mg
Nateglinide 120 mg was supplied as tablets.
DRUGAcarbose 50 mg
Acarbose 50 mg was supplied as tablets.
Sponsors
Novartis Pharmaceuticals
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
* Newly diagnosed type 2 diabetes mellitus patients * HbA1c \> 6.5 and \< 9.0% * Fasting fingertip capillary blood glucose (FCBG) \< 9 mmol/L after 2 weeks diet control
Exclusion criteria
* History of acute metabolic complications in the past 3 months or of severe diabetic complications or severe infections or active substance abuse * Liver disease * Patients under oral hypoglycemic drugs and/or insulin treatment, or corticosteroid treatment within past 4 weeks Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Postprandial Glucose Excursion (PPGE) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. PPGE was defined as the mean difference between the preprandial glucose value and the postprandial glucose value measured at 2 hours in a standardized meal test. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Postprandial Glucose Area Under the Curve at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The postprandial glucose area under the curve was calculated using values from the 4 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. |
| Change From Baseline in Total Cholesterol at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of total cholesterol prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. Total cholesterol was assessed at each study site using the same method and same reference value. |
| Change From Baseline in Triglycerides at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of triglycerides prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. Triglycerides were assessed at each study site using the same method and same reference value. |
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of LDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. LDL-C was assessed at each study site using the same method and same reference value. |
| Change From Baseline in Peak Postprandial Glucose at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The peak postprandial glucose values were used in the calculation of change from Baseline at Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. |
| Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of FFA prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. FFA was assayed at a central laboratory. |
| Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of hsCRP prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. hsCRP was assayed at a central laboratory. |
| Change From Baseline in Glycosylated Serum Albumin (GSA) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of GSA prior to (fasting) the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. GSA was assayed at a central laboratory. |
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) | Baseline to the end of the study (Week 4) | Blood samples were collected for measurement of HDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. HDL-C was assessed at each study site using the same method and same reference value. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nateglinide 120 mg Nateglinide was taken orally 3 times daily, 10 minutes before meals for 4 weeks. | 80 |
| Acarbose 50 mg Acarbose 50 mg was taken orally 3 times daily, with the first bite of food at meals for 4 weeks. | 80 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Nateglinide 120 mg | Acarbose 50 mg | Total |
|---|---|---|---|
| Age Continuous | 53.1 years STANDARD_DEVIATION 10.95 | 51.9 years STANDARD_DEVIATION 10.82 | 52.5 years STANDARD_DEVIATION 10.87 |
| Sex: Female, Male Female | 40 Participants | 33 Participants | 73 Participants |
| Sex: Female, Male Male | 40 Participants | 47 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 80 | 7 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
Primary
Change From Baseline in Postprandial Glucose Excursion (PPGE) at the End of the Study (Week 4)
Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. PPGE was defined as the mean difference between the preprandial glucose value and the postprandial glucose value measured at 2 hours in a standardized meal test. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Postprandial Glucose Excursion (PPGE) at the End of the Study (Week 4) | -1.775 mmol/L | Standard Deviation 1.3618 |
| Acarbose 50 mg | Change From Baseline in Postprandial Glucose Excursion (PPGE) at the End of the Study (Week 4) | -2.434 mmol/L | Standard Deviation 1.4418 |
Secondary
Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4)
Blood samples were collected for measurement of FFA prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. FFA was assayed at a central laboratory.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 60 minutes, N=72, 75 | -0.224 mmol/L | Standard Deviation 0.482 |
| Nateglinide 120 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 120 minutes, N=73, 75 | -0.099 mmol/L | Standard Deviation 0.605 |
| Nateglinide 120 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 90 minutes, N=72, 75 | -0.109 mmol/L | Standard Deviation 0.438 |
| Nateglinide 120 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | Fasting, N=73, 75 | -0.048 mmol/L | Standard Deviation 0.251 |
| Nateglinide 120 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 30 minutes, N=73, 75 | -0.112 mmol/L | Standard Deviation 0.427 |
| Acarbose 50 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | Fasting, N=73, 75 | -0.040 mmol/L | Standard Deviation 0.213 |
| Acarbose 50 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 30 minutes, N=73, 75 | -0.048 mmol/L | Standard Deviation 0.363 |
| Acarbose 50 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 60 minutes, N=72, 75 | -0.048 mmol/L | Standard Deviation 0.383 |
| Acarbose 50 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 90 minutes, N=72, 75 | -0.042 mmol/L | Standard Deviation 0.419 |
| Acarbose 50 mg | Change From Baseline in Free Fatty Acids (FFA) at the End of the Study (Week 4) | 120 minutes, N=73, 75 | -0.034 mmol/L | Standard Deviation 0.49 |
Secondary
Change From Baseline in Glycosylated Serum Albumin (GSA) at the End of the Study (Week 4)
Blood samples were collected for measurement of GSA prior to (fasting) the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. GSA was assayed at a central laboratory.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Glycosylated Serum Albumin (GSA) at the End of the Study (Week 4) | -1.2 Percentage | Standard Deviation 1.57 |
| Acarbose 50 mg | Change From Baseline in Glycosylated Serum Albumin (GSA) at the End of the Study (Week 4) | -1.2 Percentage | Standard Deviation 2.13 |
Secondary
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4)
Blood samples were collected for measurement of HDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. HDL-C was assessed at each study site using the same method and same reference value.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) | Fasting, N=74, 77 | 0.020 mmol/L | Standard Deviation 0.15 |
| Nateglinide 120 mg | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) | 120 minutes, N=74, 76 | 0.023 mmol/L | Standard Deviation 0.246 |
| Acarbose 50 mg | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) | Fasting, N=74, 77 | -0.039 mmol/L | Standard Deviation 0.13 |
| Acarbose 50 mg | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study (Week 4) | 120 minutes, N=74, 76 | 0.003 mmol/L | Standard Deviation 0.276 |
Secondary
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4)
Blood samples were collected for measurement of hsCRP prior to (fasting) and 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. hsCRP was assayed at a central laboratory.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 30 minutes, N=73, 75 | -0.227 mg/dL | Standard Deviation 1.232 |
| Nateglinide 120 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 90 minutes, N=72, 75 | -0.220 mg/dL | Standard Deviation 1.231 |
| Nateglinide 120 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 60 minutes, N=72, 75 | -0.219 mg/dL | Standard Deviation 1.122 |
| Nateglinide 120 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 120 minutes, N=72, 74 | -0.218 mg/dL | Standard Deviation 1.254 |
| Nateglinide 120 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | Fasting, N=73, 75 | -0.229 mg/dL | Standard Deviation 1.207 |
| Acarbose 50 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 120 minutes, N=72, 74 | 0.074 mg/dL | Standard Deviation 0.375 |
| Acarbose 50 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | Fasting, N=73, 75 | 0.080 mg/dL | Standard Deviation 0.404 |
| Acarbose 50 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 30 minutes, N=73, 75 | 0.024 mg/dL | Standard Deviation 0.135 |
| Acarbose 50 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 60 minutes, N=72, 75 | 0.071 mg/dL | Standard Deviation 0.398 |
| Acarbose 50 mg | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at the End of the Study (Week 4) | 90 minutes, N=72, 75 | 0.077 mg/dL | Standard Deviation 0.394 |
Secondary
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4)
Blood samples were collected for measurement of LDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. LDL-C was assessed at each study site using the same method and same reference value.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) | 120 minutes, N=74, 76 | -0.000 mmol/L | Standard Deviation 0.604 |
| Nateglinide 120 mg | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) | Fasting, N=74, 77 | 0.036 mmol/L | Standard Deviation 0.634 |
| Acarbose 50 mg | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) | Fasting, N=74, 77 | 0.036 mmol/L | Standard Deviation 0.57 |
| Acarbose 50 mg | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the End of the Study (Week 4) | 120 minutes, N=74, 76 | 0.044 mmol/L | Standard Deviation 0.589 |
Secondary
Change From Baseline in Peak Postprandial Glucose at the End of the Study (Week 4)
Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The peak postprandial glucose values were used in the calculation of change from Baseline at Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Peak Postprandial Glucose at the End of the Study (Week 4) | -2.350 mmol/L | Standard Deviation 1.848 |
| Acarbose 50 mg | Change From Baseline in Peak Postprandial Glucose at the End of the Study (Week 4) | -3.129 mmol/L | Standard Deviation 1.8151 |
Secondary
Change From Baseline in Postprandial Glucose Area Under the Curve at the End of the Study (Week 4)
Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The postprandial glucose area under the curve was calculated using values from the 4 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Postprandial Glucose Area Under the Curve at the End of the Study (Week 4) | -217.628 mmol*min/L | Standard Deviation 179.8929 |
| Acarbose 50 mg | Change From Baseline in Postprandial Glucose Area Under the Curve at the End of the Study (Week 4) | -278.447 mmol*min/L | Standard Deviation 171.248 |
Secondary
Change From Baseline in Total Cholesterol at the End of the Study (Week 4)
Blood samples were collected for measurement of total cholesterol prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. Total cholesterol was assessed at each study site using the same method and same reference value.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Total Cholesterol at the End of the Study (Week 4) | Fasting, N=74, 77 | 0.015 mmol/L | Standard Deviation 0.742 |
| Nateglinide 120 mg | Change From Baseline in Total Cholesterol at the End of the Study (Week 4) | 120 minutes, N=74, 76 | 0.010 mmol/L | Standard Deviation 0.7 |
| Acarbose 50 mg | Change From Baseline in Total Cholesterol at the End of the Study (Week 4) | Fasting, N=74, 77 | -0.149 mmol/L | Standard Deviation 1.05 |
| Acarbose 50 mg | Change From Baseline in Total Cholesterol at the End of the Study (Week 4) | 120 minutes, N=74, 76 | -0.059 mmol/L | Standard Deviation 0.682 |
Secondary
Change From Baseline in Triglycerides at the End of the Study (Week 4)
Blood samples were collected for measurement of triglycerides prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 4. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. Triglycerides were assessed at each study site using the same method and same reference value.
Time frame: Baseline to the end of the study (Week 4)
Population: Intent-to treat population (ITT): All randomized participants who received at least 1 dose of study drug, had valid baseline data, and at least 1 post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nateglinide 120 mg | Change From Baseline in Triglycerides at the End of the Study (Week 4) | Fasting, N=74, 77 | -0.010 mmol/L | Standard Deviation 0.737 |
| Nateglinide 120 mg | Change From Baseline in Triglycerides at the End of the Study (Week 4) | 120 minutes, N=74, 76 | 0.026 mmol/L | Standard Deviation 0.676 |
| Acarbose 50 mg | Change From Baseline in Triglycerides at the End of the Study (Week 4) | Fasting, N=74, 77 | -0.418 mmol/L | Standard Deviation 1.047 |
| Acarbose 50 mg | Change From Baseline in Triglycerides at the End of the Study (Week 4) | 120 minutes, N=74, 76 | -0.396 mmol/L | Standard Deviation 0.891 |