Effect on Beta Cell Function and Glycaemic Control After Insulin and Exenatide Sequential Therapy (T2DMRS)

Effect of Short-term Intensive Insulin Sequential Exenatide Therapy on Beta Cell Function and Glycaemic Control in Patients With Newly Diagnosed Type 2 Diabetes :a Multicenter Prospective Randomized Control Study

Whether GLP-1 receptor agonists sequential therapy in newly diagnosed type 2 diabetic patients can further improve glycemic control, diabetes remission rate and β-cell function after the short-term insulin intensive therapy.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Exenatide; Drug: Metformin

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 has been proved improving beta-cell function and usually leading to a temporary remission time,but the remission rate in a year is only about 50%. 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 an 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. Our hypotheses is whether GLP-1 receptor agonists sequential therapy in newly diagnosed type 2 diabetic patients can further improve glycemic control, diabetes remission rate and β-cell function after the short-term insulin intensive therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: xiaolong zhao, MD.; Phone Number: 86-18918067241; Email: xiaolongzhao@163.com

Study Locations

• China
  • Shanghai
    • Jingan, Shanghai, China, 20041
      • Recruiting
      • Xiaolong Zhao
      • Contact: xiaolong zhao, MD.; Phone Number: 86-18918067241; Email: xiaolongzhao@163.com
      • Principal Investigator: xiaolong zhao, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• newly diagnosed type 2 diabetes without drug treatment
• 25-70 years old age
• Fasting glucose between 7.0-16.7mmol / L
• BMI at 20 ~ 35 kg/m2 and stable for at least 3 month(weight fluctuations within three months does not exceed 10%)
• females who have no plan of pregnancy during the study

Exclusion Criteria:

• acute or chronic complications of diabetes
• myocardial infarction or cerebrovascular events within three months
• serious gastrointestinal diseases
• other serious concomitant diseases
• liver or kidney dysfunction:Transaminase (ALT and AST) greater than 3 times the upper limit of the normal range or creatinine levels greater than 133μmol / L
• GAD antibodies positive
• history of pancreatitis or pancreatic cancer;
• pregnant or breastfeeding women.
• severe hypertension (blood pressure> 180/110mmhg)
• using corticosteroids, immunosuppressants and cytotoxic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Exenatide; patients were all received a short-term intensive insulin therapy,then randomised to Exenatide group(10 ug two times a day for three months)	Drug: Exenatide; Exenatide (10 ug/bid for 3 months); Other Names: GLP-1 receptor agonist
ACTIVE_COMPARATOR: Metformin; patients were all received a short-term intensive insulin therapy,then randomised to metformin group(850mg two times a day for three months)	Drug: Metformin; Metformin 850 mg/bid for 3 months; Other Names: Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to glycaemic remission	time of glycaemic remission at 1 year after exenatide sequential therapy followed by a short-term insulin intensive treatment	up to 1 year
remission rate of type 2 diabetes at a year.	remission rate of type 2 diabetes after short-term intensive insulin and exenatide sequencial therapy	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the beta cell function change	the beta cell function change expressed by the ratio of proinsulin to insulin in fasting state and HOMA beta,the ratio of Glucose change to insulin change between at 30min and 0min time point of OGTT	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1C level at every 3 months during the whole study	HbA1C level at every 3 months during the whole study	1 year
mean glucose level during the follow without drug intervention	mean glucose level during the follow without drug intervention	1 year
number of hypoglycemia and severe hypoglycemia during the study	number of hypoglycemia and severe hypoglycemia during the study	up to 1 year

Collaborators and Investigators

• Sponsor: xiaolong zhao
• Collaborators: Shanghai Zhongshan Hospital; Second Affiliated Hospital of Soochow University; Taizhou Hospital; Shanghai Pudong New Area Gongli Hospital; Fuling Central Hospital of Chongqing City; The third people's Hospital Affiliated to Shanghai Jiao Tong University; The First Hospital of Guiyang Medical college

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ANTICIPATED): June 1, 2015
• Study Completion (ANTICIPATED): September 1, 2015

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 30, 2014
• First Posted (ESTIMATE): May 2, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): May 2, 2014
• Last Update Submitted That Met QC Criteria: April 30, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: beta cell function; the newly onset type 2 diabetes; short-term insulin treatment; exenatide sequential therapy; glycaemic remission
• 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; Metformin; Exenatide
• Other Study ID Numbers: HS2014-005