Effect of Short-Term Intensive Insulin Sequential Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients

Effect of Short-Term Intensive Insulin Sequential Exenatide Therapy on β-cell Function and Glycemic Remission Rate in Newly Diagnosed Type 2 Diabetic Patients

The randomized, controlled trial is to investigate and evaluate the effects of short-term continuous subcutaneous insulin infusion (CSII) sequential exenatide therapy on β-cell function, long-term glycemic control and glycemic remission rate in newly diagnosed type 2 diabetic patients.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: insulin lispro injection, exenatide injection; Drug: insulin lispro injection

Detailed Description

The UK Prospective Diabetes Study has shown that β-cell function progressively deteriorates over time in people with type 2 diabetes mellitus, irrespective of lifestyle and existing pharmacological interventions. The progressive nature of type 2 diabetes is one of the major challenges in the treatment of affected patients, and agents that could alter the natural history of this condition would add greatly to current treatment approaches. Short-term intensive insulin therapy of newly diagnosed type 2 diabetes will improve beta-cell function and usually leading to a temporary remission time. The effect of GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis. It is stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of ß-cell apoptosis. Exenatide is synthetic exendin-4, GLP-1 receptor agonist. Exenatide exerts direct effects on β-cell, which indicates that may contribute to delay disease progression. However, no study has evaluated effect of short-term intensive insulin sequential exenatide therapy model on β-cell function and glycemic remission rate in newly diagnosed type 2 diabetic patients. This current study is thus designed to evaluate effect of short-term intensive insulin sequential exenatide therapy model on β-cell function , glycemic control and glycemic remission rate in newly diagnosed type 2 diabetic patients.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The first afilliated hospital of Xiamen university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. newly-diagnosed type 2 diabetic patients, drug naïve
2. age 30~70 years
3. FPG 7.0~16.7mmol/L
4. BMI 20~35 kg/m2, stable body weight (≤10% variation) for at least 3 months prior to screening
5. female patients of reproductive age should practice a reliable method of birth control throughout the study

Exclusion Criteria:

1. acute or severe chronic diabetic complications
2. Recently suffered from MI or CVA.
3. severe gastrointestinal disease
4. other severe intercurrent illness
5. serum aminotransferase (ALT and AST) level higher than 2 times of the upper normal limits and/or serum creatinie≥133µmol/L (1.5mg/dL)
6. tested positive for glutamic acid decarboxylase antibody
7. use of weight loss drugs, corticosteroids, drugs known to affect gastrointestinal motility, transplantation medications, or any investigational drug
8. history of pancreatitis
9. Pregnant or lactation women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: insulin lispro injection, exenatide injection	Drug: insulin lispro injection, exenatide injection; First, Patients in the exenatide group will receive short-term continuous subcutaneous insulin (CSII)therapy. The doses will be titrated every day in order to attain the glycaemic goal which is defined as a fasting capillary blood glucose of less than 6.1 mmol/L and capillary blood glucose at 2 h after each of three meals of less than 8.0 mmol/L. Treatments will be maintained for 2 weeks after the glycaemic target will be reached. Then, patients will Sequential be treated with 5 mcg bid for 4 weeks and then 10 mcg bid for 8 weeks. After interventions will be stopped, patients will be instructed to continue diet and physical exercise only and will be followed-up with glycaemic monitoring monthly
Active Comparator: insulin lispro injection	Drug: insulin lispro injection; Patients in the control group will receive insulin with an insulin pump. The doses will be titrated every day in order to attain the glycaemic goal. Treatments will be maintained for 2 weeks after the glycaemic target will be reached. Then interventions will be stop, patients will be instructed to continue diet and physical exercise only and will be followed-up with glycaemic monitoring monthly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the glycemic remission rate in different groups	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
the improvement of β-cell function in different groups.	one year
the time of glycemic remission in different groups	one year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Investigators: Study Director: Xue-jun Li, MD,PhD, The First Affiliated Hospital of Xiamen University, China

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: January 22, 2013
• First Submitted That Met QC Criteria: January 23, 2013
• First Posted (Estimate): January 28, 2013

Study Record Updates

• Last Update Posted (Estimate): March 10, 2015
• Last Update Submitted That Met QC Criteria: March 8, 2015
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Insulin; Insulin, Globin Zinc; Insulin Lispro; Exenatide
• Other Study ID Numbers: bmd-201207-xm