AzTrials
AzTrials

Type 2 Diabetes MellitusPhase 3NCT00676338

Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

A Phase 3 study testing exenatide once weekly, metformin and sitagliptin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 106 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione) in drug naive patients with type 2 diabetes treated with diet and exercise. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
exenatide once weekly, metformin and sitagliptin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
820 participants
Where
106 sitesin 22 countries
Study dates
Nov 2008to Jan 2011
Phase
Phase 3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • have type 2 diabetes and are treated with diet and exercise alone.
  • at least 18 years of age.
  • HbA1c between 7.1% and 11.0%, inclusive.
  • Body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive.
  • Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).

Who cannot join

  • Have history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure, coronary artery bypass surgery, or angioplasty
  • Have a history of renal transplantation or are currently receiving renal dialysis
  • Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
  • Have history of severe GI disorder (e.g., gastroparesis)
  • Have a history of acute or chronic pancreatitis.
  • Have active proliferative retinopathy.
Show all 12Show fewer
  • Have been treated with drugs that promote weight loss (e.g., Xenical®[orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of screening.
  • Have been treated with any antidiabetic agent for more than 7 days within 3 months prior to screening.
  • Have had an organ transplant.
  • Have previously completed or discontinued study drug in this study, withdrawn from this study or any other study investigating exenatide once weekly.
  • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
  • Are currently enrolled in any other clinical study.

Trial locations and contacts

106 sites in 22 countries.

106 sites in 22 countries

United States18 sites
  • Research Site

    Atlanta, Georgia

  • Research Site

    Austin, Texas

  • Research Site

    Billings, Montana

  • Research Site

    Buena Park, California

  • Research Site

    Danville, Pennsylvania

  • Research Site

    Des Moines, Iowa

  • Research Site

    El Paso, Texas

  • Research Site

    Grand Rapids, Michigan

  • Research Site

    Jacksonville, Florida

  • Research Site

    Los Angeles, California

  • Research Site

    Meridian, Idaho

  • Research Site

    Minneapolis, Minnesota

  • Research Site

    New Branufels, Texas

  • Research Site

    Philadelphia, Pennsylvania

  • Research Site

    Toms River, New Jersey

  • Research Site

    Valencia, California

  • Research Site

    Wilke Barre, Pennsylvania

  • Research Site

    Wilmington, North Carolina

Other trials in United States

Canada9 sites
  • Research Site

    Coquitlam, British Columbia

  • Research Site

    Gatineu, Quebec

  • Research Site

    Mississauga

  • Research Site

    Ottawa, Ontario

  • Research Site

    Penticton, British Columbia

  • Research Site

    Petitcodiac

  • Research Site

    Pointe-Claire

  • Research Site

    Regina

  • Research Site

    Saint John

Other trials in Canada

Brazil8 sites
  • Research Site

    Brasília

  • Research Site

    Campinas

  • Research Site

    Curitiba

  • Research Site

    Fortaleza

  • Research Site

    Joinville

  • Research SIte

    Porto Alegre

  • Research Site

    Recife

  • Research Site

    São Paulo

Other trials in Brazil

United Kingdom8 sites
  • Research Site

    Bath

  • Research Site

    Birmingham

  • Research Site

    Edinburgh

  • Research Site

    Frome

  • Research Site

    Guildford

  • Research Site

    Hull

  • Research Site

    Sheffield

  • Research Site

    Swansea

Other trials in United Kingdom

India7 sites
  • Research Site

    Ahmedabad

  • Research Site

    Bangalore

  • Research Site

    Channai

  • Research Site

    Kochi

  • Research Site

    Mumbai

  • Research Site

    New Dehli

  • Research SIte

    Pune

Other trials in India

Russia5 sites
  • Research Site

    Arkhangelsk

  • Research Site

    Moscow

  • Research Site

    Rostov-on-Don

  • Research Site

    Saint Petersburg

  • Research Site

    Stavropol

Other trials in Russia

South Korea5 sites
  • Research Site

    Busan

  • Research Site

    Daegu

  • Research Site

    Jeonju

  • Research Site

    Seoul

  • Research Site

    Sungnam

Other trials in South Korea

France4 sites
  • Research Site

    Châteaugiron

  • Research Site

    Mûrs-Erigné

  • Research Site

    Nantes

  • Research Site

    Vieux-Condé

Other trials in France

Germany4 sites
  • Research Site

    Dresden

  • Research Site

    Mainz

  • Research Site

    Münster

  • Research Site

    Rodgau

Other trials in Germany

Hungary4 sites
  • Research Site

    Budapest

  • Research Site

    Gyula

  • Research Site

    Hódmezővásárhely

  • Research Site

    Pécs

Other trials in Hungary

South Africa4 sites
  • Research Site

    Johannesburg

  • Research Site

    Kempton Park

  • Research Site

    Midrand

  • Research Site

    Soweto

Other trials in South Africa

Spain4 sites
  • Research Site

    Alicante

  • Research Site

    Barcelona

  • Research Site

    Madrid

  • Research Site

    Seville

Other trials in Spain

Belgium3 sites
  • Research Site

    Leuven

  • Research Site

    Marchovelette

  • Research Site

    Tessenderlo

Other trials in Belgium

Italy3 sites
  • Research Site

    Florence

  • Research Site

    Milan

  • Research Site

    Siena

Other trials in Italy

Mexico3 sites
  • Research Site

    Chihuahua City

  • Research Site

    Guadalajara

  • Research Site

    Monterrey

Other trials in Mexico

Poland3 sites
  • Research Site

    Lublin

  • Research Site

    Szczecin

  • Research Site

    Wroclaw

Other trials in Poland

Romania3 sites
  • Research Site

    Galati

  • Research Site

    Oradea

  • Research Site

    Târgu Mureş

Other trials in Romania

Turkey (Türkiye)3 sites
  • Research Site

    Ankara

  • Research Site

    Istanbul

  • Research Site

    Sisli-Istanbul

Other trials in Turkey (Türkiye)

Argentina2 sites
  • Research Site

    Buenos Aires

  • Research Site

    Mar del Plata

Other trials in Argentina

Israel2 sites
  • Research Site

    Holon

  • Research SIte

    Tel HaShomer

Other trials in Israel

Puerto Rico2 sites
  • Research Site

    Manati

  • Research Site

    Toa Baja

Other trials in Puerto Rico

Slovakia2 sites
  • Research Site

    Bratislava

  • Research Site

    Trebišov

Other trials in Slovakia

About this study

Official title: Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes

This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione) in drug naive patients with type 2 diabetes treated with diet and exercise.

Being tested
exenatide once weekly, metformin, sitagliptin, pioglitazone
Keywords
Amylin, Lilly, exenatide once weekly, Byetta, Januvia, sitagliptin, thiazolidinedione
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • exenatide once weeklyDrug

    subcutaneous injection, 2mg, once weekly plus placebo oral once daily

  • metforminDrug

    oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection

  • sitagliptinDrug

    oral, 100 mg, daily plus placebo once weekly subcutaneous injection

  • pioglitazoneDrug

    oral, 30-45mg, daily plus placebo once weekly subcutaneous injection

Study groups in NCT00676338
Study groupRoleWhat they receive
Exenatide Once WeeklyExperimentalNot described
Receives: Drug: exenatide once weekly
MetforminActive comparatorNot described
Receives: Drug: metformin
SitagliptinActive comparatorNot described
Receives: Drug: sitagliptin
PioglitazoneActive comparatorNot described
Receives: Drug: pioglitazone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in HbA1c From Baseline to Week 26

    Change in HbA1c from baseline to Week 26.

    Measured: Baseline, Week 26

  2. Percentage of Patients Achieving HbA1c <=7% at Week 26

    Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%).

    Measured: Baseline, Week 26

Secondary outcomes (9)
  1. Change in Fasting Serum Glucose (FSG) From Baseline to Week 26

    Change in FSG from baseline to Week 26.

    Measured: Baseline, Week 26

  2. Change in Body Weight From Baseline to Week 26

    Change in Body Weight from baseline to Week 26.

    Measured: Baseline, Week 26

  3. Change in Fasting Total Cholesterol (TC) From Baseline to Week 26

    Change in Fasting TC from baseline to Week 26.

    Measured: Baseline, Week 26

  4. Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26

    Change in Fasting HDL from baseline to Week 26.

    Measured: Baseline, Week 26

  5. Ratio of Fasting Triglycerides at Week 26 to Baseline

    Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline.

    Measured: Baseline, Week 26

  6. Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events

    Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).

    Measured: Baseline to Week 26

  7. Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events

    Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).

    Measured: Baseline to Week 26

  8. Change in Systolic Blood Pressure From Baseline to Week 26.

    Change in Systolic Blood Pressure from baseline to Week 26.

    Measured: Baseline, Week 26

  9. Change in Diastolic Blood Pressure From Baseline to Week 26.

    Change in Diastolic Blood Pressure from baseline to Week 26.

    Measured: Baseline, Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionJul 2010
  4. Study completionJan 2011

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
820 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00676338
Sponsor's protocol ID
H8O-MC-GWCH (DURATION - 4)
Status last verified
Mar 2015
First submitted
9 May 2008
Last updated
9 Apr 2015
Data monitoring committee
No

Publications

  • Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.

    PubMed 32306296
  • Malloy J, Meloni A, Han J. Efficacy and tolerability of exenatide once weekly versus sitagliptin in patients with type 2 diabetes mellitus: a retrospective analysis of pooled clinical trial data. Postgrad Med. 2013 May;125(3):58-67. doi: 10.3810/pgm.2013.05.2661.

    PubMed 23748507
  • Grimm M, Han J, Weaver C, Griffin P, Schulteis CT, Dong H, Malloy J. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013 May;125(3):47-57. doi: 10.3810/pgm.2013.05.2660.

    PubMed 23748506
  • Meloni AR, DeYoung MB, Han J, Best JH, Grimm M. Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals. Cardiovasc Diabetol. 2013 Mar 23;12:48. doi: 10.1186/1475-2840-12-48.

    PubMed 23522121
  • Russell-Jones D, Cuddihy RM, Hanefeld M, Kumar A, Gonzalez JG, Chan M, Wolka AM, Boardman MK; DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012 Feb;35(2):252-8. doi: 10.2337/dc11-1107. Epub 2011 Dec 30.

    PubMed 22210563

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing exenatide once weekly, metformin and sitagliptin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 106 sites in 22 countries.

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 5 inclusion and 12 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 9 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 106 sites in United States, Canada, Brazil, United Kingdom, India and 17 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 26 Nov 2012). 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?

Change in HbA1c From Baseline to Week 26 (time frame: Baseline, Week 26). The study lists 2 primary outcomes in all. 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 NCT00676338, which also lists 5 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 9 Apr 2015.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in