Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM

Purpose

Type 2 diabetes is a systemic metabolic disease with significant morbidity and mortality due to damaging blood vessels. Increased blood sugar level is a hallmark of diabetes and is an contributes to the development of many of its complications. Multiple defects, e.g. impaired insulin secretion and impaired insulin action, contribute to the development of the disease. The aim of this study is to test the efficacy and durability of combination of drugs which correct the defects that lead to the development of diabetes on achieving adequate and durable control of blood sugar levels. Achieving adequate and durable control of blood sugar will prevent many of diabetes complications.

Condition

  • Diabetes

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • subjects with type 2 diabetes diagnosed during the past 2 years, - above 18 years of age, - drug naive, or have been on metformin less than 3 months

Exclusion Criteria

  • subjects with type 1 diabetes or GAD positive subjects or subjects with long standing diabetes (>2 years) or subjects who are not drug naive or have been on metformin more than 3 months.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Triple Therapy 		initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed
  • Drug: metformin\pioglitazone\exenatide
    metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c < 6.5%
Active Comparator
conventional therapy 		sequential addition of metformin, glyburide and basal insulin
  • Drug: metformin, glyburide and glargine
    subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c < 6.5%

More Details

Status
Completed
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Detailed Description

Subjects will be randomized (using a table of random numbers) to receive, in open label fashion, one of the following treatment regimens: (i) Group I will be started on pioglitazone (15 mg/day) plus metformin (1000 mg/day) with the supper meal and exenatide (5 mcg s.c. bid 30 min before breakfast and supper) and up-titrated to 45 pioglitazone plus 2000 metformin and 10 mcg s.c. bid exenatide to achieve HbA1c <6.0%; (II) Group II will be started on metformin, 1000 mg with breakfast and 1000 mg with supper, glyburide and basal insulin will be added and up titrated to achieve HbA1c <6.0% The study team will compare the efficacy of two therapeutic regimens: (i) triple therapy (pioglitazone, metformin, exenatide) at the time of diagnosis of T2DM versus (ii) stepwise therapy starting with metformin and subsequent addition of sulfonylurea and basal insulin (i.e., the "standard" approach) in achieving this goal. The first intervention is based on the novel concept of initiating therapy at the time of diagnosis with combination therapy using agents that correct specific pathophysiologic defects that are characteristic of T2DM (insulin resistance and beta cell failure). The second intervention is based upon stepwise addition of antidiabetic agents to reduce the HbA1C according to the current ADA therapeutic recommendation.