Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00359762
First received: July 31, 2006
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This study assesses the effects of twice-daily subcutaneous injection exenatide versus treatment with sulfonylurea (glimepiride) on long-term glycemic control and beta-cell function.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide
Drug: glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long Term Treatment With Exenatide Versus Glimepiride in Patients With Type 2 Diabetes Pretreated With Metformin (EUREXA: European Exenatide Study)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Patients With Treatment Failure [ Time Frame: Baseline to end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.

  • Time to Treatment Failure [ Time Frame: Baseline to end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.


Secondary Outcome Measures:
  • Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175).

  • Change in HOMA-B From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in HOMA-B from baseline to endpoint.

  • Fasting Proinsulin/Insulin Ratio at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3.

  • Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint. [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint.

  • Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin - fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose - fasting glucose) (measured in mmol/L).

  • Change in DI30/DG30 Ratio From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in DI30/DG30 ratio from baseline to endpoint.

  • Disposition Index at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175).

  • Change in Disposition Index From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in disposition index from baseline to endpoint.

  • Change in HbA1c From Baseline to Year 3 [ Time Frame: Baseline, Year 3 in Period II ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to Year 3.

  • Change in HbA1c From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study).

  • Fasting Plasma Glucose at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Fasting plasma glucose at Year 3.

  • Change in Fasting Plasma Glucose From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose from baseline to endpoint.

  • Postprandial (2 Hours) Plasma Glucose at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Postprandial (2 hours) plasma glucose at Year 3.

  • Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint [ Time Frame: Baseline, end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    Change from baseline in postprandial (2 hours) plasma glucose to endpoint.

  • Change in Body Weight From Baseline to Year 3 [ Time Frame: Baseline, Year 3 in Period II ] [ Designated as safety issue: No ]
    Change in Body weight from baseline to Year 3.

  • Systolic Blood Pressure at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Systolic Blood pressure at Year 3.

  • Diastolic Blood Pressure at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Diastolic Blood pressure at Year 3.

  • Heart Rate at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Heart rate at Year 3.

  • Triglycerides at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Triglycerides at Year 3.

  • Total Cholesterol at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Total Cholesterol at Year 3.

  • High-density Lipoprotein (HDL) Cholesterol at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    HDL Cholesterol at Year 3.

  • Hypoglycemia Rate Per Year [ Time Frame: Baseline to end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.

  • Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III [ Time Frame: Baseline in Period III, Year 2 in Period III ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to Year 2.

  • Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III [ Time Frame: Baseline in Period III, Year 2 in Period III ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to Year 2.

  • Hypoglycemia Rate Per Year in Period III [ Time Frame: Start of Period III to end of study ] [ Designated as safety issue: No ]
    All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.


Enrollment: 1029
Study Start Date: September 2006
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Drug: exenatide
subcutaneous injection (5mcg or 10mcg), twice a day
Other Name: Byetta
Active Comparator: Glimepiride Drug: glimepiride
oral tablet (titrated to maximally tolerated dose), once daily
Other Name: Amaryl

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with type 2 diabetes mellitus.
  • Treated with diet and exercise and a stable, maximally tolerated dose of metformin for at least 3 months prior to screening.
  • HbA1c >=6.5% and <=9.0%.
  • Body Mass Index (BMI) >=25 kg/m^2 and <40 kg/m^2.

Exclusion Criteria:

  • Participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening.
  • Characteristics contraindicating metformin or glimepiride use.
  • Receiving drugs that directly affect gastrointestinal motility.
  • Receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy.
  • Have used any prescription drug to promote weight loss within 3 months prior to screening.
  • Treated for longer than 2 weeks with any of the following medications within 3 months prior to screening: *insulin; *thiazolidinediones; *alpha-glucosidase inhibitors; *sulfonylurea; *meglitinides
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00359762

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Locations
Austria
Research Site
Graz, Austria
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Innsbruck, Austria
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Salzburg, Austria
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Vienna, Austria
Czech Republic
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Beroun, Czech Republic
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Ceske Budejovice, Czech Republic
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Hradec Kralove, Czech Republic
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Liberec, Czech Republic
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Pisek, Czech Republic
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Praha, Czech Republic
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Trebic, Czech Republic
Finland
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Helsinki, Finland
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Kuopio, Finland
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Pori, Finland
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Vaasa, Finland
France
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Alencon, France
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Bois-Guillaume, France
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Bourg des Comptes, France
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Broglie, France
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Bron, France
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Fleville Devant Nancy, France
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Le Creusot, France
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Le Mans, France
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Loudun, France
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Montigny les Metz, France
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Nevers, France
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Strasbourg, France
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Thouars, France
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Tours, France
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Valreas, France
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Vihiers, France
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Vénissieux, France
Germany
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Aschaffenburg, Germany
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Dresden, Germany
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Eisenach, Germany
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Essen, Germany
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Essen Schonnebeck, Germany
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Falkensee, Germany
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Fulda, Germany
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Hamburg, Germany
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Hamburg-Altona, Germany
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Hamburg-Ottmarschen, Germany
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Heidelberg, Germany
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Leipzig, Germany
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Munster, Germany
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Saarbrucken, Germany
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Schenklengsfeld, Germany
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Schkeuditz, Germany
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St. Ingbert, Germany
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Staffelstein, Germany
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Witten, Germany
Hungary
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Budapest, Hungary
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Gyula, Hungary
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Kecskemet, Hungary
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Veszprem, Hungary
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Zalaegerszeg, Hungary
Ireland
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County Galway, Ireland
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County Waterford, Ireland
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Dublin, Ireland
Israel
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Haifa, Israel
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Holon, Israel
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Jerusalem, Israel
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Tel Hashomer, Israel
Italy
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Ancona, Italy
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Arenzano, Italy
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Atri, Italy
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Bergamo, Italy
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Catanzaro, Italy
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Firenze, Italy
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Foggia, Italy
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Forli, Italy
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Genova, Italy
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Grosseto, Italy
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Milano, Italy
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Monserrato (Cagliari), Italy
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Napoli, Italy
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Palermo, Italy
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Perugia, Italy
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Pescara, Italy
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Pisa, Italy
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Ravenna, Italy
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Roma, Italy
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San Benedetto del Tronto, Italy
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Siena, Italy
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Treviso, Italy
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Verona, Italy
Mexico
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Mexico City, Distrito Federal, Mexico
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Celaya, Guanajuato, Mexico
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Pachuca, Hidalgo, Mexico
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Monterrey, Nuevo Leon, Mexico
Poland
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Bialystok, Poland
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Bydgoszcz, Poland
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Lublin, Poland
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Szczecin, Poland
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Warszawa, Poland
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Wroclaw, Poland
Spain
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Barcelona, Spain
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Madrid, Spain
Switzerland
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Fribourg, Switzerland
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Geneva, Switzerland
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Geneve, Switzerland
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Lausanne, Switzerland
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Luzern, Switzerland
United Kingdom
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Bath, United Kingdom
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Belfast, United Kingdom
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Brandford on Avon, United Kingdom
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County Antrim, United Kingdom
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Downpatrick, United Kingdom
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Frome, United Kingdom
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Midsomer Norton, United Kingdom
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Omagh, United Kingdom
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Penzance, United Kingdom
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Plymouth, United Kingdom
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Southdown, United Kingdom
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Wiltshire, United Kingdom
Sponsors and Collaborators
AstraZeneca
Eli Lilly and Company
Investigators
Study Director: James Malone, MD Eli Lilly and Company
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00359762     History of Changes
Other Study ID Numbers: H8O-EW-GWBE
Study First Received: July 31, 2006
Results First Received: March 29, 2012
Last Updated: June 6, 2014
Health Authority: Austria: Federal Ministry for Health and Women
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Mexico: Ministry of Health
Poland: Ministry of Health
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medical Board

Keywords provided by AstraZeneca:
exenatide
diabetes
Amylin
Lilly
glimepiride

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Glimepiride
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 16, 2014