Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Nateglinide, Pancreatic beta cell function
Brief summary
This multi-center, randomized controlled study aims to evaluate the durability and efficacy of nateglinide therapy for long term glycemic control compared with glimepiride.
Detailed description
Selected patients will be randomly assigned to receive nateglinide or glimepiride. Previous treatment with oral antidiabetic drugs (metformin, a-glucosidase inhibitor, nateglinide or sulfonylurea) will be discontinued. After a 1 month wash-out period (if 6.5 ≤ HbA1c ≤ 8.5), patients will take randomly assigned drugs for 24 months. Patients will be met by the trial investigator every 3 months following randomization. At each visit, patients whose HbA1c is \> 8.0% will be retested 2 weeks later, and if the retested HbA1c is also above 8.0%, those patients will be withdrawn considering monotherapy failure. We will evaluate the durability of nateglinide in comparison with that of glimepiride based on the withdrawal rate.
Interventions
DRUGNateglinide
Nateglinide 90\ 120mg three times a day
DRUGGlimepiride
Glimepiride 1\ 2mg once a day
Sponsors
Korea University Guro Hospital
Hanyang University
Inha University Hospital
Kyunghee University Medical Center
Myongji Hospital
Bundang CHA Hospital
Wonju Severance Christian Hospital
Hallym University Medical Center
Ajou University School of Medicine
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
* type 2 diabetes mellitus * age\>=18years * no anti hyperglycemic agent for 3 months or low-dose oral hypoglycemic therapy * metformin≤1g/day, acarbose≤300mg/day, voglibose≤0.9mg/day, nateglinide≤270mg/day, gliclazide≤80mg/day, glimepiride≤2mg/day, glibenclamide≤5mg/day (nateglinide or sulfonylurea \<6months) * 6.5% ≤ HbA1c ≤ 8.5% * patients on no anti hyperglycemic agent for 3 months : HbA1c at screening * patients on oral hypoglycemic therapy in 3months : HbA1c after wash-out
Exclusion criteria
* attending other clinical trials in 3months * type I diabetes mellitus * taking systemic steroid in 1month or requiring steroid therapy during clinical trial * acute myocardial infarction in 6months * alcoholics, pituitary or adrenal insufficiency, severe ketosis, diabetic ketoacidosis * severe liver disease or AST, ALT ≥ 2.5 x ULN * renal insufficiency (serum creatinine \> 2.0mg/dl) * other severe diabetic complication * drug hypersensitivity history to nateglinide or sulfonylurea * pregnant or plan to become pregnant during the clinical trial, lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate | every 3 months following randomization, for 24 months | % monotherapy failure, that means % number of participants who withdrew from the study due to high HbA1c (\>8.0%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c | at 24 months | HbA1c (%) at 24 months |
| Fasting Glucose | at 24 months | fasting glucose (mg/dL) at 24 months |
| C-peptide | at 24 months | c-peptide(uU/mL) at 24 months |
| HOMA-IR | at 24 months | insulin resistance marker HOMA-IR at 24 months |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nateglinide Nateglinide 90\
120mg three times a day
Nateglinide: Nateglinide 90\
120mg three times a day | 46 |
| Glimepiride Glimepiride 1\
2mg once a day
Glimepiride: Glimepiride 1\
2mg once a day | 42 |
| Total | 88 |
Baseline characteristics
| Characteristic | Nateglinide | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 10.5 | 55.1 years STANDARD_DEVIATION 12.3 | 55 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 23 Participants | 18 Participants | 41 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 6 / 24 | 1 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate
% monotherapy failure, that means % number of participants who withdrew from the study due to high HbA1c (\>8.0%)
Time frame: every 3 months following randomization, for 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nateglinide | The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate | 10 Participants |
| Glimepiride | The Durability of Nateglinide in Comparison With Those of Glimepiride Based on the Withdrawal Rate | 7 Participants |
Secondary
C-peptide
c-peptide(uU/mL) at 24 months
Time frame: at 24 months
Population: data of participants who finished 24 months of follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide | C-peptide | 1.29 uU/mL | Standard Deviation 0.41 |
| Glimepiride | C-peptide | 1.77 uU/mL | Standard Deviation 0.72 |
Secondary
Fasting Glucose
fasting glucose (mg/dL) at 24 months
Time frame: at 24 months
Population: data of participants who finished 24 months of follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide | Fasting Glucose | 131.2 mg/dL | Standard Deviation 25.9 |
| Glimepiride | Fasting Glucose | 115.7 mg/dL | Standard Deviation 19.8 |
Secondary
HbA1c
HbA1c (%) at 24 months
Time frame: at 24 months
Population: data of participants who finished 24 months of follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide | HbA1c | 6.9 % HbA1c | Standard Deviation 0.6 |
| Glimepiride | HbA1c | 6.5 % HbA1c | Standard Deviation 0.5 |
Secondary
HOMA-IR
insulin resistance marker HOMA-IR at 24 months
Time frame: at 24 months
Population: data of participants who finished 24 months of follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nateglinide | HOMA-IR | 2.40 mg/dL x mIU/L | Standard Deviation 1.36 |
| Glimepiride | HOMA-IR | 2.31 mg/dL x mIU/L | Standard Deviation 1.7 |