Clinical trial NCT00676338: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Amylin
Lilly
exenatide once weekly
Byetta
Januvia
sitagliptin
thiazolidinedione
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2008-05-13
Enrollment: 820
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Patients Achieving HbA1c <=7% at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change in Fasting Serum Glucose (FSG) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in Body Weight From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in Fasting Total Cholesterol (TC) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Ratio of Fasting Triglycerides at Week 26 to Baseline
timeFrame: Baseline, Week 26
measure: Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
timeFrame: Baseline to Week 26
measure: Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events
timeFrame: Baseline to Week 26
measure: Change in Systolic Blood Pressure From Baseline to Week 26.
timeFrame: Baseline, Week 26
measure: Change in Diastolic Blood Pressure From Baseline to Week 26.
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Buena Park
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Valencia
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Meridian
country: United States
facility: Research Site
state: Idaho
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Billings
country: United States
facility: Research Site
state: Montana
city: Toms River
country: United States
facility: Research Site
state: New Jersey
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Danville
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Wilke Barre
country: United States
facility: Research Site
state: Pennsylvania
city: Austin
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: New Branufels
country: United States
facility: Research Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Marchovelette
country: Belgium
facility: Research Site
city: Tessenderlo
country: Belgium
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Campinas
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Joinville
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research SIte
city: Recife
country: Brazil
facility: Research Site
city: Sao Paolo
country: Brazil
facility: Research Site
city: Coquitlam
country: Canada
facility: Research Site
state: British Columbia
city: Penticton
country: Canada
facility: Research Site
state: British Columbia
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Gatineu
country: Canada
facility: Research Site
state: Quebec
city: Mississauga
country: Canada
facility: Research Site
city: Petitcodiac
country: Canada
facility: Research Site
city: Pointe-Claire
country: Canada
facility: Research Site
city: Regina
country: Canada
facility: Research Site
city: Saint John
country: Canada
facility: Research Site
city: Chateaugiron
country: France
facility: Research Site
city: Murs Erigne
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Vieux Conde
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Rodgau
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Hodmezovasarhely
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Channai
country: India
facility: Research Site
city: Cochin
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: New Dehli
country: India
facility: Research Site
city: Pune
country: India
facility: Research SIte
city: Holon
country: Israel
facility: Research Site
city: Tel-Hashomer
country: Israel
facility: Research SIte
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Jeonju
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Sungnam
country: Korea, Republic of
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Manati
country: Puerto Rico
facility: Research Site
city: Toa Baja
country: Puerto Rico
facility: Research Site
city: Galati
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Stavropol
country: Russian Federation
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Trebisov
country: Slovakia
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Kempton Park
country: South Africa
facility: Research Site
city: Midrand
country: South Africa
facility: Research Site
city: Soweto
country: South Africa
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Sisli-Istanbul
country: Turkey
facility: Research Site
city: Bath
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Frome
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Eli Lilly and Company
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.