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)

NCT00676338 | Completed Phase 3 Results

• 1 other identifier: H8O-MC-GWCH (DURATION - 4)
• Study Type: interventional
• Target: 820
• Locations: 22 countries
• Sites: 106

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Amylin; Lilly; exenatide once weekly; Byetta; Januvia; sitagliptin; thiazolidinedione

Outcome Measures

Primary Outcomes (2)

• Change in HbA1c From Baseline to Week 26

  Change in HbA1c from baseline to Week 26.

  Baseline, Week 26

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

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

  Baseline, Week 26

Secondary Outcomes (9)

• Change in Fasting Serum Glucose (FSG) From Baseline to Week 26

  Baseline, Week 26

• Change in Body Weight From Baseline to Week 26

  Baseline, Week 26

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

  Baseline, Week 26

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

  Baseline, Week 26

• Ratio of Fasting Triglycerides at Week 26 to Baseline

  Baseline, Week 26

Study Arms (4)

Exenatide Once Weekly

EXPERIMENTAL

Drug: exenatide once weekly

Metformin

ACTIVE COMPARATOR

Drug: metformin

Sitagliptin

ACTIVE COMPARATOR

Drug: sitagliptin

Pioglitazone

ACTIVE COMPARATOR

Drug: pioglitazone

Interventions

exenatide once weekly DRUG

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

Exenatide Once Weekly

metformin DRUG

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

Metformin

sitagliptin DRUG

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

Sitagliptin

pioglitazone DRUG

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

Pioglitazone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (106)

Research Site

Buena Park, California, United States

Location

Research Site

Los Angeles, California, United States

Location

Research Site

Valencia, California, United States

Location

Research Site

Jacksonville, Florida, United States

Location

Research Site

Atlanta, Georgia, United States

Location

Research Site

Meridian, Idaho, United States

Location

Research Site

Des Moines, Iowa, United States

Location

Research Site

Grand Rapids, Michigan, United States

Location

Research Site

Minneapolis, Minnesota, United States

Location

Research Site

Billings, Montana, United States

Location

Research Site

Toms River, New Jersey, United States

Location

Research Site

Wilmington, North Carolina, United States

Location

Research Site

Danville, Pennsylvania, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Wilke Barre, Pennsylvania, United States

Location

Research Site

Austin, Texas, United States

Location

Research Site

El Paso, Texas, United States

Location

Research Site

New Branufels, Texas, United States

Location

Research Site

Buenos Aires, Argentina

Location

Research Site

Mar del Plata, Argentina

Location

Research Site

Leuven, Belgium

Location

Research Site

Marchovelette, Belgium

Location

Research Site

Tessenderlo, Belgium

Location

Research Site

Brasília, Brazil

Location

Research Site

Campinas, Brazil

Location

Research Site

Curitiba, Brazil

Location

Research Site

Fortaleza, Brazil

Location

Research Site

Joinville, Brazil

Location

Research SIte

Porto Alegre, Brazil

Location

Research Site

Recife, Brazil

Location

Research Site

São Paulo, Brazil

Location

Research Site

Coquitlam, British Columbia, Canada

Location

Research Site

Penticton, British Columbia, Canada

Location

Research Site

Ottawa, Ontario, Canada

Location

Research Site

Gatineu, Quebec, Canada

Location

Research Site

Mississauga, Canada

Location

Research Site

Petitcodiac, Canada

Location

Research Site

Pointe-Claire, Canada

Location

Research Site

Regina, Canada

Location

Research Site

Saint John, Canada

Location

Research Site

Châteaugiron, France

Location

Research Site

Mûrs-Erigné, France

Location

Research Site

Nantes, France

Location

Research Site

Vieux-Condé, France

Location

Research Site

Dresden, Germany

Location

Research Site

Mainz, Germany

Location

Research Site

Münster, Germany

Location

Research Site

Rodgau, Germany

Location

Research Site

Budapest, Hungary

Location

Research Site

Gyula, Hungary

Location

Research Site

Hódmezővásárhely, Hungary

Location

Research Site

Pécs, Hungary

Location

Research Site

Ahmedabad, India

Location

Research Site

Bangalore, India

Location

Research Site

Channai, India

Location

Research Site

Kochi, India

Location

Research Site

Mumbai, India

Location

Research Site

New Dehli, India

Location

Research SIte

Pune, India

Location

Research Site

Holon, Israel

Location

Research SIte

Tel Litwinsky, Israel

Location

Research Site

Florence, Italy

Location

Research Site

Milan, Italy

Location

Research Site

Siena, Italy

Location

Research Site

Chihuahua City, Mexico

Location

Research Site

Guadalajara, Mexico

Location

Research Site

Monterrey, Mexico

Location

Research Site

Lublin, Poland

Location

Research Site

Szczecin, Poland

Location

Research Site

Wroclaw, Poland

Location

Research Site

Manatí, Puerto Rico

Location

Research Site

Toa Baja, Puerto Rico

Location

Research Site

Galati, Romania

Location

Research Site

Oradea, Romania

Location

Research Site

Târgu Mureş, Romania

Location

Research Site

Arkhangelsk, Russia

Location

Research Site

Moscow, Russia

Location

Research Site

Rostov-on-Don, Russia

Location

Research Site

Saint Petersburg, Russia

Location

Research Site

Stavropol, Russia

Location

Research Site

Bratislava, Slovakia

Location

Research Site

Trebišov, Slovakia

Location

Research Site

Johannesburg, South Africa

Location

Research Site

Kempton Park, South Africa

Location

Research Site

Midrand, South Africa

Location

Research Site

Soweto, South Africa

Location

Research Site

Busan, South Korea

Location

Research Site

Daegu, South Korea

Location

Research Site

Jeonju, South Korea

Location

Research Site

Seoul, South Korea

Location

Research Site

Sungnam, South Korea

Location

Research Site

Alicante, Spain

Location

Research Site

Barcelona, Spain

Location

Research Site

Madrid, Spain

Location

Research Site

Seville, Spain

Location

Research Site

Ankara, Turkey (Türkiye)

Location

Research Site

Istanbul, Turkey (Türkiye)

Location

Research Site

Sisli-Istanbul, Turkey (Türkiye)

Location

Research Site

Bath, United Kingdom

Location

Research Site

Birmingham, United Kingdom

Location

Research Site

Edinburgh, United Kingdom

Location

Research Site

Frome, United Kingdom

Location

Research Site

Guildford, United Kingdom

Location

Research Site

Hull, United Kingdom

Location

Research Site

Sheffield, United Kingdom

Location

Research Site

Swansea, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 32306296 DERIVED

• 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.

  PMID: 23748507 DERIVED

• 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.

  PMID: 23748506 DERIVED

• 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.

  PMID: 23522121 DERIVED

• 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.

  PMID: 22210563 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Sitagliptin Phosphate; Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Thiazolidinediones; Thiazoles; Sulfur Compounds

Results Point of Contact

• Title: Peter Ohman, Medical Science Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Chief Medical Officer, MD

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2008
• First Posted: May 13, 2008
• Study Start: November 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: January 1, 2011
• Last Updated: April 9, 2015
• Results First Posted: November 26, 2012

Record last verified: 2015-03

Locations

BE (3); PL (3); DE (4); HU (4); IL (2); IT (3); CA (9); FR (4); AR (2); BR (8); RO (3); SL (2); ME (3); ZA (4); KR (5); RU (5); ES (4); TU (3); PR (2); GB (8); US (18); IN (7)