Diabetes Mellitus, Type 2, Newly Diagnosed
Conditions
Keywords
diabetes mellitus, type 2, newly diagnosed, exenatide, premixed insulin analog, thiazolidinedione, β-cell function, glycemic control
Brief summary
The purpose of this study is to investigate and evaluate the effects of different interventions (1. exenatide, 2. insulin, 3. thiazolidinedione) on glycemic control and β-cell function in newly diagnosed drug-naïve type 2 diabetic patients.
Detailed description
One of the fundamental defects in type 2 diabetes mellitus is declining β-cell function. Exenatide targets multiple metabolic disturbances in type 2 diabetes and exerts direct effects on β-cell, which indicates that it may not only contribute to the glucose control but also delay disease progression. There are trials demonstrated efficacy, safety and tolerability of exenatide. However, no study has compared the effects of exenatide with other hypoglycemic therapies with β cell protective function in newly diagnosed and drug-naïve type 2 diabetic patients. This current study is thus designed to evaluate the effects of exenatide, insulin and pioglitazone on glycemic control and β-cell function in newly diagnosed drug-naïve type 2 diabetic patients.
Interventions
Patients in exenatide group will be treated with exenatide (Byetta®, Eli Lilly and Company) 5 µg BID for the first 4 weeks and then 10 µg BID thereafter.
DRUGMixed Protamine Zinc Recombinant Human Insulin Lispro 25R
Patients in insulin group will be treated with premixed insulin analog (Humalog Mix 25, Eli Lilly and Company). The initial insulin doses are 0.4 IU/kg per day(50% before breakfast and 50% before dinner). Insulin doses are titrated following a forced schedule according to blood glucose before breakfast and dinner.
DRUGPioglitazone
Patients in thiazolidinedione group will be treated with Pioglitazone 30mg daily as single dose. The dose will be increased to 45mg daily after 4 weeks.
Sponsors
Eli Lilly and Company
Amylin Pharmaceuticals, LLC.
Ministry of Health, China
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* newly-diagnosed type 2 diabetic patients, drug naïve * age 30\ 70 years * HbA1c 7.0\ 10.0% * BMI 20\ 35 kg/m2, stable body weight (≤10% variation) for at least 3 months prior to screening * female patients of reproductive age should practice a reliable method of birth control throughout the study
Exclusion criteria
* acute or severe chronic diabetic complications * congestive heart failure (NYHA grade Ⅲ\ Ⅳ) * severe gastrointestinal disease * severe osteoporosis or history of pathological fracture,or use of bisphosphonates preparation * other severe intercurrent illness * serum aminotransferase (ALT and AST) level higher than 2 times of the upper normal limits and/or serum creatinie≥133µmol/L (1.5mg/dL) * tested positive for glutamic acid decarboxylase antibody * use of weight loss drugs, corticosteroids, drugs known to affect gastrointestinal motility, transplantation medications, or any investigational drug * history of pancreatitis * serum triglyceride ≥ 5.0 mmol/L * pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks | 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients Achieving HbA1c <7% and ≤ 6.5% and Effect of Different Interventions on Fasting and Postprandial Plasma Glucose Concentration, Blood Pressure, Lipid Profiles | 48 weeks |
| β-cell Function (Acute Insulin Response During IVGTT; HOMA-B, Disposition Index and Proinsulin/Insulin Ratio) | 48 weeks |
| Safety and Tolerability in Different Groups | 48 weeks |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide | 142 |
| Premixed Insulin Analog | 138 |
| Thiazolidinedione | 136 |
| Total | 416 |
Baseline characteristics
| Characteristic | Premixed Insulin Analog | Thiazolidinedione | Total | Exenatide |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 7 Participants | 27 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 128 Participants | 129 Participants | 389 Participants | 132 Participants |
| Age Continuous | 51.39 years STANDARD_DEVIATION 9.65 | 49.66 years STANDARD_DEVIATION 8.86 | 50.31 years STANDARD_DEVIATION 9.4 | 49.89 years STANDARD_DEVIATION 9.64 |
| Region of Enrollment China | 138 participants | 136 participants | 416 participants | 142 participants |
| Sex: Female, Male Female | 53 Participants | 53 Participants | 150 Participants | 44 Participants |
| Sex: Female, Male Male | 85 Participants | 83 Participants | 266 Participants | 98 Participants |
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 | 69 / 142 | 42 / 138 | 43 / 136 |
| serious Total, serious adverse events | 5 / 142 | 1 / 138 | 7 / 136 |
Outcome results
Primary
the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks | -1.8 percentage of HbA1c | Standard Deviation 1.29 |
| Premixed Insulin Analog | the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks | -1.74 percentage of HbA1c | Standard Deviation 1.16 |
| Thiazolidinedione | the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks | -1.47 percentage of HbA1c | Standard Deviation 1.3 |
p-value: <0.05ANCOVA
Secondary
Percentage of Patients Achieving HbA1c <7% and ≤ 6.5% and Effect of Different Interventions on Fasting and Postprandial Plasma Glucose Concentration, Blood Pressure, Lipid Profiles
Time frame: 48 weeks
Secondary
Safety and Tolerability in Different Groups
Time frame: 48 weeks
Secondary
β-cell Function (Acute Insulin Response During IVGTT; HOMA-B, Disposition Index and Proinsulin/Insulin Ratio)
Time frame: 48 weeks