DiabetesPhase 4NCT01107717
Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM
A Phase 4 study testing metformin\pioglitazone\exenatide and metformin, glyburide and glargine in people with Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetes
- What is being tested?
- metformin\pioglitazone\exenatide and metformin, glyburide and glargine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 318 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to 3 Feb 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Texas Diabetes Institute
San Antonio, Texas, 78229-3900
About this study
Official title: Durability of Early Initial Combination Therapy With Exenatide/Pioglitazone/Metformin vs Conventional Therapy in New Onset Type 2 Diabetes
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.
Read the 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
- Being tested
- metformin\pioglitazone\exenatide, metformin, glyburide and glargine
- Keywords
- type 2 diabetes, new onset, combination therapy, new onset type 2 diabetes
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin\pioglitazone\exenatideDrug
metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c < 6.5%
metformin, glyburide and glargineDrug
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%
| Study group | Role | What they receive |
|---|---|---|
| Triple Therapy | Experimental | initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed Receives: Drug: metformin\pioglitazone\exenatide |
| conventional therapy | Active comparator | sequential addition of metformin, glyburide and basal insulin Receives: Drug: metformin, glyburide and glargine |
What is being measured
The primary outcome is the main question the study is designed to answer.
HbA1c Level
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
Measured: at the end of the study (3 years)
Secondary outcomes (2)
Treatment Failure
Number of participants with HbA1c>6.5% at 3 years
Measured: 3 years
Percentage of Patients With Reported Hypoglycemic Events
asymptomatic hypoglycemic events with documented PGC < 60 mg/dl and sympotomatic hypoglycemia
Measured: during the entire study (3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2010 (estimated)
- Study startJan 2009
- Primary completion3 Feb 2023
- Study completion3 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association, Amylin Pharmaceuticals, LLC., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Ralph DeFronzo, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01107717
- Sponsor's protocol ID
- HSC20080456H
- Other IDs
- 5R01DK103841-03
- Status last verified
- Aug 2024
- First submitted
- 19 Apr 2010
- Last updated
- 5 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Deidentified data will be shared with local investigators
Publications
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.
PubMed 33273042Abdul-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.
PubMed 40288809
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durability of Early Initial Combination Therapy With Exenatide/Pioglitazone/Metformin vs Conventional Therapy in New Onset Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01107717
- Acronym / sponsor ID
- HSC20080456H
- Conditions
- Diabetes
- Keywords
- type 2 diabetes, new onset, combination therapy, new onset type 2 diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- American Diabetes Association, Amylin Pharmaceuticals, LLC., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jan 2009
- Primary completion
- 3 Feb 2023 (actual)
- Study completion
- 3 Feb 2023 (actual)
- First posted
- 21 Apr 2010 (estimated)
- Results
- Posted 5 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Triple Therapy | Experimental | Drug: metformin\pioglitazone\exenatideinitiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed |
| conventional therapy | Active comparator | Drug: metformin, glyburide and glarginesequential addition of metformin, glyburide and basal insulin |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metformin\pioglitazone\exenatidemetformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c < 6.5% | Drug | Triple Therapy |
| metformin, glyburide and glarginesubjects 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% | Drug | conventional therapy |
Primary outcome
HbA1c Level
Time frame: at 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
2 secondary outcomes
Treatment Failure
Time frame: 3 years
Percentage of Patients With Reported Hypoglycemic Events
Time frame: during the entire study (3 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33273042Abdul-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.
- Derived from this study: PubMed 40288809Abdul-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.
- Individual participant dataSharing planned: Yes. Deidentified data will be shared with local investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralph DeFronzo, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing metformin\pioglitazone\exenatide and metformin, glyburide and glargine in people with Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HbA1c Level (time frame: at the end of the study (3 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01107717, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.