Clinical trial NCT01107717: Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM
Official title: Durability of Early Initial Combination Therapy With Exenatide/Pioglitazone/Metformin vs Conventional Therapy in New Onset Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes
Keywords: type 2 diabetes
new onset
combination therapy
new onset type 2 diabetes
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
name: Amylin Pharmaceuticals, LLC.
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2010-04-21
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: HbA1c Level
timeFrame: at the end of the study (3 years)
Secondary outcomes:
measure: Treatment Failure
timeFrame: 3 years
measure: Percentage of Patients With Reported Hypoglycemic Events
timeFrame: during the entire study (3 years)
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Texas Diabetes Institute
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Ralph DeFronzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abdul-Ghani M, Puckett C, Adams J, Khattab A, Baskoy G, Cersosimo E, Triplitt C, DeFronzo RA. Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT. Diabetes Care. 2021 Feb;44(2):433-439. doi: 10.2337/dc20-0978. Epub 2020 Dec 3.