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

NCT ID: NCT01107717

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 318 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2023-02-03

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.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Triple Therapy

initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed

Group Type: EXPERIMENTAL

metformin\pioglitazone\exenatide

Intervention Type: DRUG

metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%

conventional therapy

sequential addition of metformin, glyburide and basal insulin

Group Type: ACTIVE_COMPARATOR

metformin, glyburide and glargine

Intervention Type: DRUG

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%

Interventions

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%

Intervention Type: 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%

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Amylin Pharmaceuticals, LLC.

INDUSTRY

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph DeFronzo, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

Texas Diabetes Institute

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 33273042 (View on PubMed)

Abdul-Ghani M, Puckett C, Abdelgani S, Merovci A, Lavrynenko O, Adams J, Triplitt C, DeFronzo RA. Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT study. BMJ Open Diabetes Res Care. 2025 Apr 27;13(2):e004981. doi: 10.1136/bmjdrc-2025-004981.

Reference Type: DERIVED

PMID: 40288809 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

5R01DK103841-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC20080456H

Identifier Type: -

Identifier Source: org_study_id