Type 2 Diabetes MellitusPhase 3NCT00097500

Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

A Phase 3 study testing exenatide, Insulin glargine and Metformin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This Phase 3, open-label, multicenter study is designed to compare the effects of exenatide and insulin glargine (Lantus® injection) on beta-cell function in patients with type 2 diabetes mellitus using metformin. Read more about this study

Who is it for?: Ages 30 to 75 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: exenatide, Insulin glargine and Metformin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: 3 sitesin 3 countries
Study dates: Sep 2004to Dec 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of type 2 diabetes, but otherwise healthy
HbA1c between 6.6% and 9.5%, inclusive.
Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive.
Treated with a stable dose of metformin for at least 2 months prior to screening.

Who cannot join

Patients previously in a study using exenatide.
Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening).
Treated with insulin within 3 months of screening.

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

Finland1 site

Research Site
Helsinki

Other trials in Finland

Netherlands1 site

Research Site
Amsterdam

Other trials in Netherlands

Sweden1 site

Research Site
Gothenburg

Other trials in Sweden

About this study

Official title: A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metformin Who Have Not Achieved Target HbA1c

Conditions: Type 2 Diabetes Mellitus
Being tested: exenatide, Insulin glargine, Metformin
Keywords: diabetes, exenatide, exendin-4, Amylin, Lilly
Medical subject headings: Diabetes Mellitus, Type 2, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

exenatideDrug
Also called Byetta
subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets
Insulin glargineDrug
Also called Lantus
subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets
MetforminDrug
Patients usual dosage

Study groups in NCT00097500
Study group	Role	What they receive
Exenatide Arm	Experimental	Exenatide and Metformin Receives: Drug: exenatide; Drug: Metformin
Insulin Glargine Arm	Active comparator	Insulin Glargine and Metformin Receives: Drug: Insulin glargine; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

Beta-cell Function After 52 Weeks of Therapy
Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).
Measured: Baseline (week -2) and 52 weeks

Secondary outcomes (8)

Beta-cell Function 4 Weeks After Cessation of Therapy
Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]).
Measured: Baseline (week -2) and 56 weeks
Change in First Phase C-peptide Release
Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.
Measured: baseline (week -2), 52 weeks, and 56 weeks
Change in Second Phase C-peptide Release
Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.
Measured: baseline (-2 weeks), 52 weeks, and 56 weeks
Change in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).
Measured: Week 0 and week 52
Change in Fasting Plasma Glucose
Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).
Measured: 0 weeks and 52 weeks
Seven Point Self Monitored Blood Glucose (SMBG) Measurements
SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).
Measured: 0 weeks and 52 weeks
Change in Body Weight
Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).
Measured: 0 weeks and 52 weeks
M-value at Baseline, Week 52 and Week 56
M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.
Measured: baseline (week -2), 52 weeks, and 56 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2004Dec 2009

First posted25 Nov 2004 (estimated)
Study startSep 2004
Primary completionDec 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00097500
Sponsor's protocol ID: 2993-114
Status last verified: Mar 2015
First submitted: 24 Nov 2004
Last updated: 7 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009 May;32(5):762-8. doi: 10.2337/dc08-1797. Epub 2009 Feb 5.
PubMed 19196887
Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
PubMed 39963952
Muskiet MHA, Bunck MC, Heine RJ, Corner A, Yki-Jarvinen H, Eliasson B, Joles JA, Diamant M, Tonneijck L, van Raalte DH. Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial. Diabetes Res Clin Pract. 2019 Jul;153:14-22. doi: 10.1016/j.diabres.2019.05.001. Epub 2019 May 9.
PubMed 31078666
Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Jarvinen H, Diamant M. Effects of exenatide on measures of beta-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011 Sep;34(9):2041-7. doi: 10.2337/dc11-0291.
PubMed 21868779
Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Wu Y, Yan P, Smith U, Yki-Jarvinen H, Diamant M, Taskinen MR. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010 Sep;212(1):223-9. doi: 10.1016/j.atherosclerosis.2010.04.024. Epub 2010 Apr 29.
PubMed 20494360

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metformin Who Have Not Achieved Target HbA1c
ClinicalTrials.gov ID: NCT00097500
Acronym / sponsor ID: 2993-114
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes, exenatide, exendin-4, Amylin, Lilly
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Sep 2004
Primary completion: Dec 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 25 Nov 2004 (estimated)
Results: Posted 10 Jan 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Exenatide Arm	Experimental	Drug: exenatide, Drug: MetforminExenatide and Metformin
Insulin Glargine Arm	Active comparator	Drug: Insulin glargine, Drug: MetforminInsulin Glargine and Metformin

Who may qualify

Ages: 30 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Diagnosis of type 2 diabetes, but otherwise healthy
HbA1c between 6.6% and 9.5%, inclusive.
Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive.
Treated with a stable dose of metformin for at least 2 months prior to screening.

Key exclusion criteria (3 listed)

Patients previously in a study using exenatide.
Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening).
Treated with insulin within 3 months of screening.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
exenatideAlso: Byettasubcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets	Drug	Exenatide Arm
Insulin glargineAlso: Lantussubcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets	Drug	Insulin Glargine Arm
MetforminPatients usual dosage	Drug	Exenatide Arm, Insulin Glargine Arm

Primary outcome

Beta-cell Function After 52 Weeks of Therapy
Time frame: Baseline (week -2) and 52 weeks
Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).

8 secondary outcomes

Beta-cell Function 4 Weeks After Cessation of Therapy
Time frame: Baseline (week -2) and 56 weeks
Change in First Phase C-peptide Release
Time frame: baseline (week -2), 52 weeks, and 56 weeks
Change in Second Phase C-peptide Release
Time frame: baseline (-2 weeks), 52 weeks, and 56 weeks
Change in Glycosylated Hemoglobin (HbA1c)
Time frame: Week 0 and week 52
Change in Fasting Plasma Glucose
Time frame: 0 weeks and 52 weeks
Seven Point Self Monitored Blood Glucose (SMBG) Measurements
Time frame: 0 weeks and 52 weeks
Change in Body Weight
Time frame: 0 weeks and 52 weeks
M-value at Baseline, Week 52 and Week 56
Time frame: baseline (week -2), 52 weeks, and 56 weeks

Results and safety

Results posted to the registry on 10 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide Arm	36	30
Insulin Glargine Arm	33	30

Primary outcome: Beta-cell Function After 52 Weeks of Therapy

Time frame: Baseline (week -2) and 52 weeks. Least squares mean (Standard Error). Unit: ratio

Measure	Exenatide Arm n = 30	Insulin Glargine Arm n = 30
Value	2.89 (0.27)	1.15 (0.11)

Exenatide Arm vs Insulin Glargine Arm: p = 0.0001, ANCOVA

Population analysed: Evaluable population

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Total reporting period for adverse events is 64 weeks: a 52-week on-drug period followed by a 12-week off-drug period.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide Arm	3 of 36 (8.3%)	32 of 36 (88.9%)	Not reported
Insulin Glargine Arm	1 of 33 (3%)	31 of 33 (93.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19196887Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009 May;32(5):762-8. doi: 10.2337/dc08-1797. Epub 2009 Feb 5.
Derived from this study: PubMed 39963952Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
Derived from this study: PubMed 31078666Muskiet MHA, Bunck MC, Heine RJ, Corner A, Yki-Jarvinen H, Eliasson B, Joles JA, Diamant M, Tonneijck L, van Raalte DH. Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial. Diabetes Res Clin Pract. 2019 Jul;153:14-22. doi: 10.1016/j.diabres.2019.05.001. Epub 2019 May 9.
Derived from this study: PubMed 21868779Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Jarvinen H, Diamant M. Effects of exenatide on measures of beta-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011 Sep;34(9):2041-7. doi: 10.2337/dc11-0291.
Derived from this study: PubMed 20494360Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Wu Y, Yan P, Smith U, Yki-Jarvinen H, Diamant M, Taskinen MR. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010 Sep;212(1):223-9. doi: 10.1016/j.atherosclerosis.2010.04.024. Epub 2010 Apr 29.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vice President, Research and Development, MD study director

Amylin Pharmaceuticals, LLC.

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing exenatide, Insulin glargine and Metformin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Finland, Netherlands, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jan 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Beta-cell Function After 52 Weeks of Therapy (time frame: Baseline (week -2) and 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00097500, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2015.