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CompletedPhase 3Results posted

Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Effect of AC2993 (Synthetic Exendin-4) Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Lead sponsor

AstraZeneca

Asset

Exenatide

Subcutaneous · GLP-1 agonist

Listed sites

91

Recruiting sites

Enrollment

551

actual

Study population

Type 2 diabetes

Key I/E criterion

HbA1c 7-10%

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 IDNCT00082381
Org study IDH8O-MC-GWAA

Timeline

Milestones

Study first posted2004-05-11estimated
Results first posted2013-07-31estimated
Last update posted2015-04-07estimated
Study start2003-06 (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 one of the following for at least 3 months prior to screening: 1. 1500 to 2550 mg/day immediate-release metformin (or 1500 to 2000 mg/day extended-release metformin) and at least an optimally effective dose of a 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 10.0%, inclusive.
History of stable body weight (not varying by >10% for at least three months prior to screening).
Female patients are not breastfeeding, and female patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause)

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 participated in this study previously or any other study using AC2993 or GLP-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 are undergoing therapy for a malignancy, other than basal cell or squamous cell skin 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 insulin glargine, AC2993, or excipients contained in these agents.
Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label, in the opinion of the investigator.
Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.3 mg/dL for females.
Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamicpyruvic transaminase greater than three times the upper limit of the reference range.
Patients have known hemoglobinopathy or chronic anemia.
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 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 26

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), kg95% CI
Exenatide ArmBaseline body weight88.42
Change in body weight at week 26-2.32
Insulin Glargine ArmBaseline body weight89.25
Change in body weight at week 261.75
p<0.0001ANCOVA

Glycemic / diabetes

4 endpoints
Primary/protocol endpoint

Change in Glycosylated Hemoglobin (HbA1c)

Time frame:Baseline, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

GroupValue (least_squares_mean), percentage95% CI
Exenatide ArmBaseline HbA1c8.13
Change in HbA1c at week 26-1.00
Insulin Glargine ArmBaseline HbA1c8.19
Change in HbA1c at week 26-1.05
Mean Difference (Final Values)0.0595% CI-0.090.20p0.4602ANCOVA
Secondary/protocol endpoint

Percentage of Patients Achieving HbA1c <=7%

Time frame:26 weeks

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

GroupValue (number), percentage of participants95% CI
Exenatide Arm46.43
Insulin Glargine Arm48.03
p0.7839Fisher Exact
Secondary/protocol endpoint

Change in Fasting Serum Glucose

Time frame:Baseline, week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

GroupValue (least_squares_mean), mmol/L95% CI
Exenatide ArmBaseline fasting serum glucose10.27
Change in fasting serum glucose at week 26-1.22
Insulin Glargine ArmBaseline fasting serum glucose10.46
Change in fasting serum glucose at week 26-2.86
p<0.0001ANCOVA
Secondary/protocol endpoint

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

Time frame:Baseline, week 26

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), mmol/L95% CI
Exenatide ArmPre-breakfast: Baseline SMBG9.47
Pre-breakfast: Change in SMBG at week 26-1.25
2hr post breatfast: Baseline SMBG12.51
2hr post breakfast: Change in SMBG at week 26-3.77
Pre-lunch: Baseline SMBG9.61
Pre-lunch: Change in SMBG at week 26-1.50
2hr post lunch: Baseline SMBG11.15
2hr post lunch: Change in SMBG at week 26-1.68
Pre-dinner: Baseline SMBG9.46
Pre-dinner: Change in SMBG at week 26-1.15
2hr post dinner: Baseline SMBG11.17
2hr post dinner: Change in SMBG at week 26-3.06
3:00 AM: Baseline SMBG9.02
3:00 AM: Change in SMBG at week 26-1.05
Insulin Glargine ArmPre-breakfast: Baseline SMBG9.50
Pre-breakfast: Change in SMBG at week 26-2.56
2hr post breatfast: Baseline SMBG12.36
2hr post breakfast: Change in SMBG at week 26-2.86
Pre-lunch: Baseline SMBG9.47
Pre-lunch: Change in SMBG at week 26-1.93
2hr post lunch: Baseline SMBG10.96
2hr post lunch: Change in SMBG at week 26-1.69
Pre-dinner: Baseline SMBG9.35
Pre-dinner: Change in SMBG at week 26-1.72
2hr post dinner: Baseline SMBG11.49
2hr post dinner: Change in SMBG at week 26-1.65
3:00 AM: Baseline SMBG9.36
3:00 AM: Change in SMBG at week 26-1.97

Safety / tolerability / PK

2 endpoints
Secondary/protocol endpoint

Percentage of Patients With Hypoglycemic Events

Time frame:26 weeks

Documented hypoglycemia

threshold achievement, event

Posted result

GroupValue (number), percentage of participants95% CI
Exenatide Arm55.32
Insulin Glargine Arm59.93
p0.3002Fisher Exact
Secondary/protocol endpoint

Change in Rate of Hypoglycemic Events

Time frame:Baseline, week 26

Documented hypoglycemia

change from baseline, event

Posted result

GroupValue (least_squares_mean), events per 30 days per patient95% CI
Exenatide ArmBaseline event rate0.09
Change in event rate at week 260.23
Insulin Glargine ArmBaseline event rate0.11
Change in event rate at week 260.29
p0.3385ANCOVA

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.

Registry references + supporting bibliography

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.