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

Phase 4
Completed
Conditions
Diabetes
Interventions
Drug: metformin\pioglitazone\exenatide
Drug: metformin, glyburide and glargine
Registration Number
NCT01107717
Lead Sponsor
The University of Texas Health Science Center at San Antonio
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
521
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Triple Therapymetformin\pioglitazone\exenatideinitiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed
conventional therapymetformin, glyburide and glarginesequential addition of metformin, glyburide and basal insulin
Primary Outcome Measures
NameTimeMethod
HbA1c Levelat the end of the study (3 years)

subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study

Secondary Outcome Measures
NameTimeMethod
Treatment Failure3 years

Number of participants with HbA1c\>6.5% at 3 years

Percentage of Patients With Reported Hypoglycemic Eventsduring the entire study (3 years)

asymptomatic hypoglycemic events with documented PGC \< 60 mg/dl and sympotomatic hypoglycemia

Trial Locations

Locations (1)

Texas Diabetes Institute

🇺🇸

San Antonio, Texas, United States

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