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CompletedPhase 3Results posted

Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

Efficacy of Exenatide (AC2993, Synthetic Exendin-4, LY2148568) Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

Lead sponsor

AstraZeneca

Asset

Exenatide

Subcutaneous · GLP-1 agonist

Listed sites

69

Recruiting sites

Enrollment

505

actual

Study population

Type 2 diabetes

Key I/E criteria

BMI 25-40HbA1c 7-11%

Primary endpoint

HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT00082407
Org study IDH8O-MC-GWAD

Timeline

Milestones

Study first posted2004-05-10estimated
Results first posted2013-07-31estimated
Last update posted2015-04-07estimated
Study start2003-11 (month precision)
Primary completion2008-07actual (month precision)
Study completion2008-07actual (month precision)

Assets

Investigational agents

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age30 Years
Maximum age75 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. >=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components
HbA1c between 7.0% and 11.0%, inclusive.
Patients have a body mass index >25kg/m2 and <40 kg/m2.
Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control

Exclusion criteria

Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study.
Patients are employed by Lilly or Amylin.
Patients have previously, in this or any other study, received exenatide or glucagon-like peptide-1 analogs.
Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
Patients have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer).
Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
Patients have a known allergy or hypersensitivity to biphasic insulin aspart, exenatide, or excipients contained in these agents.
Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label.
Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females.
Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range.
Patients have known hemoglobinopathy or chronic anemia.
Patients have active proliferative retinopathy or macular edema.
Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
Patients have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides.
Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
Patients fail to satisfy the investigator of suitability to participate for any other reason.

Endpoints (7)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes
4
Safety / tolerability / PK
2
Weight & body composition
1

Weight & body composition

1 endpoint
Secondary/protocol endpoint

Change in Body Weight

Time frame:baseline, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), kg95% CI
Exenatide ArmBaseline body weight85.51
Change in body weight at week 52-2.54
Biphasic Insulin Aspart ArmBaseline body weight83.38
Change in body weight at week 522.92
p0.0001ANCOVA

Glycemic / diabetes

4 endpoints
Primary/protocol endpoint

Change in Glcosylated Hemoglobin (HbA1c)

Time frame:baseline, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

GroupValue (least_squares_mean), percentage95% CI
Exenatide ArmBaseline HbA1c8.59
Change in HbA1c at week 52-0.98
Biphasic Insulin Aspart ArmBaseline HbA1c8.65
Change in HbA1c at week 52-0.88
Mean Difference (Final Values)-0.1095% CI-0.280.08p0.2534ANCOVA
Secondary/protocol endpoint

Percentage of Patients Achieving HbA1c <=7%

Time frame:52 weeks

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

GroupValue (number), percentage of participants95% CI
Exenatide Arm31.7
Biphasic Insulin Aspart Arm24.1
p0.0779Fisher Exact
Secondary/protocol endpoint

Change in Fasting Serum Glucose

Time frame:baseline, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

GroupValue (least_squares_mean), mmol/L95% CI
Exenatide ArmBaseline fasting serum glucose11.00
Change in fasting serum glucose at week 52-1.75
Biphasic Insulin Aspart ArmBaseline fasting serum glucose11.30
Change in fasting serum glucose at week 52-1.64
p0.6456ANCOVA
Secondary/protocol endpoint

Change in 7-point Self-monitored Blood Glucose (SMBG) Profile

Time frame:baseline, week 52

Postprandial glucose

change from baseline, improvement

Posted result

GroupValue (mean), mmol/L95% CI
Exenatide ArmPre-breakfast: Baseline SMBG9.57
Pre-breakfast: Change in SMBG at week 52-1.15
After breakfast: Baseline SMBG12.30
After breakfast: Change in SMBG at week 52-3.83
Pre-lunch: Baseline SMBG9.38
Pre-lunch: Change in SMBG at week 52-1.47
After lunch: Baseline SMBG11.18
After lunch: Change in SMBG at week 52-1.72
Pre-dinner: Baseline SMBG9.35
Pre-dinner: Change in SMBG at week 52-1.06
After dinner: Baseline SMBG11.25
After dinner: Change in SMBG at week 52-3.11
3:00 AM: Baseline SMBG9.08
3:00 AM: Change in SMBG at week 52-0.96
Biphasic Insulin Aspart ArmPre-breakfast: Baseline SMBG9.86
Pre-breakfast: Change in SMBG at week 52-1.68
After breakfast: Baseline SMBG12.71
After breakfast: Change in SMBG at week 52-3.06
Pre-lunch: Baseline SMBG9.86
Pre-lunch: Change in SMBG at week 52-2.40
After lunch: Baseline SMBG11.39
After lunch: Change in SMBG at week 52-1.76
Pre-dinner: Baseline SMBG9.57
Pre-dinner: Change in SMBG at week 52-1.52
After dinner: Baseline SMBG11.68
After dinner: Change in SMBG at week 52-2.44
3:00 AM: Baseline SMBG9.58
3:00 AM: Change in SMBG at week 52-1.95

Safety / tolerability / PK

2 endpoints
Secondary/protocol endpoint

Percentage of Patients With Hypoglycemic Events

Time frame:52 weeks

Documented hypoglycemia

threshold achievement, event

Posted result

GroupValue (number), percentage of participants95% CI
Exenatide Arm53.0
Biphasic Insulin Aspart Arm51.6
p0.7888Fisher Exact
Secondary/protocol endpoint

Change in Rate of Hypoglycemic Events

Time frame:baseline, week 52

Documented hypoglycemia

change from baseline, event

Posted result

GroupValue (least_squares_mean), events per 30 days per patient95% CI
Exenatide ArmBaseline event rate0.22
Change in event rate at week 520.19
Biphasic Insulin Aspart ArmBaseline event rate0.18
Change in event rate at week 520.26
p0.3722ANCOVA

Publications (3)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.