Evaluation of the Effects of Different Interventions on Glycemic Control in Newly-Diagnosed Type 2 Diabetic Patients

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT00147836

Collaborator

Ministry of Education, China (Other), Guangdong Science and Technology Bureau, China (Other), Hoffmann-La Roche (Industry), Novo Nordisk A/S (Industry)

436

Enrollment

Location

Arms

Duration (Months)

11.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate and evaluate the effects of different interventions (1.continuous subcutaneous insulin infusion,2.multiple daily injections, 3.anti-hyperglycemic agents) on glycemic control, B-cell function and the remission rate in newly-diagnosed type 2 diabetic patients.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Human Insulin (Novolin-R, Novo Nordisk) Device: H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland Other: Pre-meal Drug: Novolin-R Drug: Human Insulin NPH (Novolin-N, Novo Nordisk) Drug: Gliclazide (Diamicron, Servier) Drug: Diamicron and Glucophage	N/A

Detailed Description

ß-Cell dysfunction and decreased insulin sensitivity are the main pathophysiological defects responsible for the development of hyperglycemia. With continuous presence of insulin resistance, progressive loss of ß-cell function is the crucial defect. Hyperglycemia has deleterious effect on β-cell function, which is partially reversible by adequate glycemic control. In newly diagnosed type 2 diabetic patients with severe hyperglycemia, 2 weeks continuous subcutaneous insulin infusion (CSII) can induce adequate glycemic control with improvement of β-cell function. Nearly half of the patients can maintain euglycemia longer than 12 months by transient CSII. The improvement of β-cell function, especially the restoration of the first-phase insulin response is related to sustained euglycemia in the newly diagnosed type 2 diabetic patients. But it is unclear whether any other interventions (such as oral hypoglycemic agents and multiple daily injections) inducing optimal glycemic control in a short period of time can have the same effect. As a multicenter, open-label, randomized, parallel-group study will be needed to further prove and clarify the findings.

Study Design

Study Type:

Interventional

Actual Enrollment :

436 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Effects of Oral Anti-Hyperglycemic Agents, Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion on Glycemic Control, B-Cell Function and the Remission Rate in Newly-Diagnosed Type 2 Diabetic Patients

Study Start Date :

Sep 1, 2004

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CSII Patients in continuous subcutaneous insulin infusion group received Human Insulin (Novolin-R, Novo Nordisk) with an insulin pump (H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland);	Drug: Human Insulin (Novolin-R, Novo Nordisk) Device: H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland
Active Comparator: MDI Patients in MDI group were treated with pre-meal Novolin-R, and Human Insulin NPH (Novolin-N, Novo Nordisk) at bedtime. Initial insulin doses were 0.4-0.5 IU/kg and total daily doses were divided into 50% of basal and 50% of bolus injection in CSII group and 30%-20%-20%-30% in multiple daily insulin injection group	Other: Pre-meal Drug: Novolin-R Drug: Human Insulin NPH (Novolin-N, Novo Nordisk)
Active Comparator: OHA In oral hpoglycemic agents group, the patients with 20 kg/m2<BMI≤25kg/m2 were initiated with Gliclazide (Diamicron, Servier) 80mg Bid (maximum to 160mg Bid), the patients with 25kg/m2<BMI≤35kg/m2 were initiated with Metformin (Glucophage, BMS) 0.5 Bid (maximum to 2.0g/d), the combination of Diamicron and Glucophage was used in patients who could not achieve glycaemic control goal with one OHA or with FPG≥11.1mmol/l at randomization	Drug: Gliclazide (Diamicron, Servier) Drug: Diamicron and Glucophage

Arm

Intervention/Treatment

Active Comparator: CSII

Patients in continuous subcutaneous insulin infusion group received Human Insulin (Novolin-R, Novo Nordisk) with an insulin pump (H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland);

Drug: Human Insulin (Novolin-R, Novo Nordisk)

Device: H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland

Active Comparator: MDI

Patients in MDI group were treated with pre-meal Novolin-R, and Human Insulin NPH (Novolin-N, Novo Nordisk) at bedtime. Initial insulin doses were 0.4-0.5 IU/kg and total daily doses were divided into 50% of basal and 50% of bolus injection in CSII group and 30%-20%-20%-30% in multiple daily insulin injection group

Other: Pre-meal

Drug: Novolin-R

Drug: Human Insulin NPH (Novolin-N, Novo Nordisk)

Active Comparator: OHA

In oral hpoglycemic agents group, the patients with 20 kg/m2<BMI≤25kg/m2 were initiated with Gliclazide (Diamicron, Servier) 80mg Bid (maximum to 160mg Bid), the patients with 25kg/m2<BMI≤35kg/m2 were initiated with Metformin (Glucophage, BMS) 0.5 Bid (maximum to 2.0g/d), the combination of Diamicron and Glucophage was used in patients who could not achieve glycaemic control goal with one OHA or with FPG≥11.1mmol/l at randomization

Drug: Gliclazide (Diamicron, Servier)

Drug: Diamicron and Glucophage

Outcome Measures

Primary Outcome Measures

glycemic control, the improvement of β-cell l function and the remission rate after short intensive therapy in newly diagnosed type 2 diabetic patients [Oct. 2007]

Secondary Outcome Measures

the effects of different interventions (oral anti-hyperglycemic agents, multiple daily injections and continuous subcutaneous insulin infusion) on glycemic control, β-cell function and the remission rate in newly-diagnosed type 2 diabetic patients [Oct. 2007]

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

informed consents be given before treatment
the newly-diagnosed type 2 diabetic patients
fasting blood glucose (FBG) level ranging from 7.0～16.7 mmol/L
age ranging from 25～70 years old
body mass index (BMI) ranging from20～35kg/m2
never be treated with any anti-hyperglycemic agents or anti-hyperlipidemic agents

Exclusion Criteria:

having any severe acute or chronic complications
renal dysfunction, blood creatinine≥150µmol/L
blood aminotransferase level rising up(more than 2 times of the normal level)
any severe cardiac disease including congestive cardiac failure, unstable angina and myocardial infarct in 12 months
serious hypertension (systolic pressure≥180mmHg and/ or diastolic pressure≥110mmHg)
chronic or acute pancreatic disease
severe systematic diseases or malignant tumor
allergic to the drugs using in the trial
any factors interfering the result
female patients incline to be pregnant
being treated with corticosteroid, immunosuppressing drugs or cytotoxic drugs
poor compliance