The Effects of Short-Term Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients
Information source: Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes
Intervention: Exenatide (Drug); Humulin-N (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Taipei Veterans General Hospital, Taiwan Official(s) and/or principal investigator(s): Harn-Shen Chen, MD, PhD, Principal Investigator, Affiliation: Taipei Veterans General Hospital, Taiwan
Summary
Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement in beta-cell
function following short-term therapy is currently not known. This randomized, controlled
trial is carried to assess the efficacy of short-term insulin therapy (NPH injection twice
daily) compared with GLP-1 analogue (Exenatide injection twice daily) on glycemic control,
remission rate, ß-cell function, and long-term glycemic control in newly diagnosed type 2
diabetic patients with moderate hyperglycemia.
Clinical Details
Official title: The Effects of Short-Term Exenatide Therapy on the Beta-Cell Function and Long-term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: the time of glycemic remission and remission rateThe time of monotherapy failure and monotherapy failure rate
Secondary outcome: Beta-cell function and insulin sensitivity calculated from OGTT.Comparison of A1C change, the proportion of subjects who reached the treatment target Comparison of A1C change, the proportion of subjects who reached the treatment target
Detailed description:
Background: There is a progressive deterioration in beta-cell function in type 2 diabetics,
and it was estimated that islet function was about 50% of normal at the time of diagnosis.
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 acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is
stimulation of glucose-dependent insulin release, followed by enhancement of insulin
biosynthesis and stimulation of insulin gene transcription. The chronic action is
stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of ß-cell
apoptosis, thus promoting expansion of beta-cell mass, as observed in rodent diabetes and in
cultured beta-cells.
Objectives: Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement
in beta-cell function following short-term therapy is currently not known. This randomized,
controlled trial is carried to assess the efficacy of short-term insulin therapy (NPH
injection twice daily) compared with GLP-1 analogue (Exenatide injection twice daily) on
glycemic control, remission rate, beta-cell function, and long-term glycemic control in
newly diagnosed type 2 diabetic patients with moderate hyperglycemia.
Study Designs and Methods: We will recruit 80 newly diagnosed type 2 diabetic patients with
moderate hyperglycemia, and another 80 newly diagnosed type 2 diabetic patients with severe
hyperglycemia who receive intensive insulin therapy for 10-14 days, and will be randomized
to be treated with exenatide or insulin injections. They will visit our clinics every 2
weeks in the first 2 visits and then every 4 weeks for 20 weeks. After the 24 weeks of
intervention, all patients will be treated with life style modification only and follow
fasting plasma glucose every month. Hyperglycemia relapse is defined as fasting plasma
glucose more than 126 mg/dL and confirmed two weeks later. Patients with hyperglycemia
relapse will be treated with metformin (from 500 mg per day to 1500 mg per day)and then
gliclazide-MR will be added to as the second step for the remaining study period. A1C
measurement will be performed at baseline, 3, 6, 12 and 18 months, and OGTT will be
performed at screen and after 6 months of randomization. All of these subjects were
continually followed-up in our clinics for 5 years to evaluate their long-term glycemic
control. The monotherapy failure is defined as A1C >7. 0% with metformin 1500 mg/day.
The primary outcomes at one year are the time of glycemic remission and remission rate at
one year after short-term therapy. The primary outcomes at 5 years are monotherapy failure
time and monotherapy failure rate at 5 years after short-term therapy. The secondary
outcomes are the beta-cell function and insulin sensitivity calculated from OGTT, the
comparison of A1C change, the proportion of subjects who reached the treatment target (A1C
<7. 0% or <6. 5% at 1 and 5 years). These subjects will be followed up for 5 years to evaluate
their long-term glycemic control.
Expected Results: We will expect to screen 100 patients, randomize 80 patients and there
will be at least 30 patients in each group complete the one year follow-up. We expected that
short-term intensive treated with both insulin and exenatide can get better glycemic control
accompanied with improving the beta-cell function in newly diagnosed type 2 diabetes. We can
compare the remission rate at one year after different short-term therapy. We will further
evaluate the effects on the beta-cell function and long-term glycemic control. This study
also can assess what readily available parameter would predict which patients will achieve
long-term successful glycemic control after correction of glucose toxicity.
Eligibility
Minimum age: 30 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Newly diagnosed type 2 diabetic patients.
2. Age between 30 and 70 years old.
3. HbA1C between 7 and 9% in OPD patients
4. If HbA1c >9. 0% of blood glucose >300 mg/dL, intensive insulin therapy for 10-14 days
Exclusion Criteria:
1. Previous treated with anti-diabetic medication
2. Pregnant or lactation women.
3. Impaired liver function (ALT > 100 U/L)
4. Impaired renal function (Serum creatinine >2. 0 mg/dL)
5. Recently suffered from MI or CVA.
6. Patients are acute intercurrent illness.
7. 2-hour C-peptide level < 2. 0 ng/mL.
8. History of severe hypersensitivity to any product components.
9. History or high risk of acute pancreatitis.
10. Now use warfarin.
Locations and Contacts
Taipei Veterans General Hospital, Taipei 11217, Taiwan; Recruiting Harn-Shen Chen, MD, PhD, Phone: 886-2-28757515, Email: chenhs@vghtpe.gov.tw Harn-Shen Chen, MD, PhD, Principal Investigator
Additional Information
Starting date: November 2010
Last updated: June 26, 2013
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