A Comparison of Exenatide and Insulin Glargine
Study Details
Study Description
Brief Summary
This is a 16-week, Single-center, Randomized, Open Label, Parallel Controlled Group Comparison of the Comprehensive Glycemic Control of Exenatide and Insulin Glargine on Type 2 Diabetes Patients Inadequately Controlled With Metformin Monotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Screening will be made to select eligible patients, then 44 patients receiving a stable dose of metformin (≥1500 mg daily) will be randomized (1:1) to receive exenatide or insulin glargine for 16 weeks. Exenatide will be administered twice daily by subcutaneous injection 30- 60 minutes before breakfast and dinner; the dose was 5 μg twice-daily for the first 4 weeks of treatment and 10 μg thereafter. Insulin glargine will be administered once daily at bedtime by subcutaneous injection. The dose of insulin glargine will initiate at ≥8 IU once-daily, and titrate based on a dosing algorithm targeting fasting blood glucose (FPG)<6.1 mmol/L. Titration is only allowed in first 4 weeks. At the end of the study, data will be collected and analyzed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: exenatide 5 μg BID for the first 4 weeks of treatment and 10 μg thereafter |
Drug: exenatide
5 μg BID for the first 4 weeks of treatment and 10 μg thereafter.
Other Names:
Drug: Insulin glargine
≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks.
Other Names:
|
| Active Comparator: Insulin glargine ≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks. |
Drug: exenatide
5 μg BID for the first 4 weeks of treatment and 10 μg thereafter.
Other Names:
Drug: Insulin glargine
≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean amplitude of glycemic excursions (MAGE) change from baseline by continuous glucose monitoring system (CGMS) [1±3day；112±3d]
Secondary Outcome Measures
- Glycemic variability [1±3day；112±3d]
continuous overlapping net glycemic action (CONGA) and mean of daily differences (MODD)
- Glucose control [-7±3d；112±3d；]
Glycosylated hemoglobin A 1c (HbA1c), FBG, postprandial blood glucose (PBG)
- oxidative stress markers [1±3d；28±3d；56±3d；84±3d；112±3d]
plasma concentrations of superoxide dismutase (SOD), malondialdehyde, 8-iso-prostaglandin-F2α (8-iso-PGF2α) and urine concentrations of 8-iso-PGF2α;
- inflammatory markers [1±3d；28±3d；56±3d；84±3d；112±3d]
plasma concentrations of interleukin-1(IL-1), interleukin-18(IL-18), adiponectin, toll-like receptor 4(TLR-4) and phosphorylated-nuclear factor-kappaB 65 (pNF-κB 65) in white blood cells
- endothelial function [1±3d；28±3d；56±3d；84±3d；112±3d]
plasma total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), nitric oxide (NO)
- beta-cell function and insulin resistance [1±3d；112±3d；]
homeostasis model assessment-β, homeostasis model assessment -insulin resistance, plasma glucagon, body mass index (BMI), waist-hip ratio
- body composition [1±3d；112±3d]
fat mass, lean tissue, body weight, waist circumference
Other Outcome Measures
- Number of Participants with exenatide or insulin glargine adverse events as a measure of safety and tolerability: [-7±3d；1±3d；7±2d；14±3d；21±2d；28±3d；35±3d；56±3d；84±3d；112±3d]
hypoglycemia reaction; blood glucose lower than 3.1mmol/L; nausea, vomiting, diarrhea, anorexia or abdominal pain after exenatide subcutaneous injection.
- Exploratory Objective assessed by the relationships between oxidative stress and inflammatory markers and MAGE [1±3d；112±3d]
Whether there is linear correlation between oxidative stress markers and MAGE, and between inflammatory markers and MAGE, and correlation coefficient of each correlation
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Provision of informed consent prior to any study specific procedures
-
Type2 diabetic patients had been on stable, maximum tolerated doses of metformin (≧1500mg/d, ≧8 weeks)
-
Male or female age ≧ 18 years and ≦70 years old
-
HbA1c ≧7.0 and ≦10%
-
BMI ≧ 24 kg/m2
Exclusion Criteria:
-
Known or suspected allergy to trial products or related products.
-
Impaired renal function defined as serum-creatinine ≥ 1.5 mg/dl (≥ 133 umol/l).
-
Acute or chronic disease which may cause tissue hypoxia such as respiratory failure or shock.
-
Abnormal liver function, alanine transaminase or aspartate aminotransferase ≥ 3 fold normal upper limit, Total bilirubin ≥ 2 normal upper limit, acute alcohol intoxication, alcoholism.
-
Subjects has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association-class Ⅲ and Ⅳ).
-
Proliferative retinopathy or muscular oedema requiring acute treatment.
-
Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception (adequate contraceptive measures are sterilization, intrauterine device, oral contraceptives or barrier methods).
-
Treatment with systemic corticosteroids within the past two months prior to screening.
-
Type 1 diabetes mellitus.
-
Receipt of any investigational drug within 1 month prior to this trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University | Nanjing | Jiangsu | China | 210008 |
Sponsors and Collaborators
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Investigators
- Principal Investigator: Dalong Zhu, MD PhD, the Affiliated Drum Tower Hospital of Nanjing University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ISSEXEN0034