Type 2 Diabetes MellitusPhase 3NCT00960661
A Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes
A Phase 3 study testing exenatide, insulin lispro and Metformin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 95 sites in 18 countries.
Trial summary
The study will compare two combination therapies: 1) Combined Basal Insulin Glargine (once a day), Exenatide (twice a day), and Metformin Therapy; or 2) Combined Basal Insulin Glargine (once a day), Bolus Insulin Lispro (three times a day), and Metformin Therapy, in subjects with Type 2 Diabetes Mellitus who have… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- exenatide, insulin lispro and Metformin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,036 participants
- Where
- 95 sitesin 18 countries
- Study dates
- Sep 2009to Aug 2012
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have been taking a basal insulin Glargine, at dose of ≥ 20 units/day, for at least 3 months prior to study start.
- Have been taking basal insulin Glargine at dose of ≥ 20 units/day, in combination with 1 of the following oral antidiabetic medication (OAM) regimens, for at least 3 months prior to study start:
- Metformin or immediate-release metformin or extended-release metformin alone at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to study start; or
- Metformin or immediate-release metformin or extended-release metformin at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to study start and sulfonylurea at a stable dose for 6 weeks prior to study start.
- Have an HbA1C > 7.0% and ≤ 10.0%.
- Have a body mass index (BMI) between ≥ 25 and ≤ 45 kg/m2.
Who cannot join
- Are currently taking OAM that is not described above and not allowed with concurrent use of insulin per local product label.
- Have taken more than 1 week within 1 month prior to the study start any glucose-lowering medications not included above either alone or in combination formulations, or have used a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phenylpropanolamine, rimonabant or similar over-the-counter medications).
- Have taken any insulin other than Glargine within the 3 months prior to study start for more than 1 week.
- Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, and inhaled preparations) within 4 weeks prior to the study start.
- Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
- Have previously completed or been withdrawn from this study after enrollment.
Trial locations and contacts
95 sites in 18 countries.
95 sites in 18 countries
France16 sites
Research Site
Angers
Research Site
Auxerre
Research Site
Bar-le-Duc
Research Site
Douai
Research Site
La Roche-sur-Yon
Research Site
La Rochelle
Research Site
Le Creuzot
Research Site
Lille
Research Site
Marseille
Research Site
Montpellier
Research Site
Nanterre
Research Site
Pessac
Research Site
Rennes
Research Site
Strasbourg
Research Site
Toulouse
Research Site
Vénissieux
Argentina8 sites
Research Site
Buenos Aires
Research Site
Caba
Research Site
Capital Federal
Research Site
Ciudad Autonoma de Buenos Aire
Research Site
Ciudad de Buenos Aires
Research Site
Corrientes
Research Site
Rosario
Research Site
San Rafael
Germany8 sites
Research Site
Bad Lauterberg im Harz
Research Site
Dippoldiswalde
Research Site
Friedrichsthal
Research Site
Goch
Research Site
Grevenbroich
Research Site
Hamburg
Research Site
Mainz
Research Site
Saarbrücken
Netherlands8 sites
Research Site
Almere Stad
Research Site
Amsterdam
Research Site
Beek
Research Site
Groningen
Research Site
Heerlen
Research Site
Hoogeveen
Research Site
Sittard-Geleen
Research Site
The Hague
Sweden7 sites
Research Site
Halmstad
Research Site
Karlstad
Research Site
Lund
Research Site
Malmö
Research Site
Solna
Research Site
Stockholm
Research Site
Umeå
Italy6 sites
Research Site
Florence
Research Site
Naples
Research Site
Olbia
Research Site
Perugia
Research Site
Trieste
Research Site
Verona
Romania6 sites
Research Site
Bucharest
Research Site
Cluj-Napoca
Research Site
Constanța
Research Site
Craiova
Research Site
Oradea
Research Site
Ploieşti
Spain6 sites
Research Site
A Coruña
Research Site
Alicante
Research Site
Barcelona
Research Site
Dos Hermanas
Research Site
Santander
Research Site
Valencia
United Kingdom5 sites
Research Site
Bournemouth
Research Site
Ipswich
Research Site
Leicester
Research Site
Penarth
Research Site
Wakefield
Belgium4 sites
Research Site
Arlon
Research Site
Bonheiden
Research Site
Edegem
Research Site
Merksem
Mexico4 sites
Research Site
Aguascalientes
Research Site
Cuernavaca
Research Site
Mexico City
Research Site
Monterrey
Portugal3 sites
Research Site
Coimbra
Research Site
Lisbon
Research Site
Portugal
Russia3 sites
Research Site
Arkhangelsk
Research Site
Rostov-on-Don
Research Site
Saint Petersburg
South Korea3 sites
Research Site
Seoul
Research Site
Ulsan
Research Site
Wŏnju
About this study
Official title: A Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Insulin Glargine With Either Metformin or Metformin and Sulfonylurea
The study will compare two combination therapies: 1) Combined Basal Insulin Glargine (once a day), Exenatide (twice a day), and Metformin Therapy; or 2) Combined Basal Insulin Glargine (once a day), Bolus Insulin Lispro (three times a day), and Metformin Therapy, in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- exenatide, insulin lispro, Metformin, Insulin/ Glargine
- Keywords
- diabetes, exenatide, Byetta, insulin lispro, Humalog, insulin glargine, Lantus, 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, 5mcg (4 weeks) followed by 10mcg (26 weeks), twice a day
insulin lisproDrug
Also called Humalog
titrated based on pre-meal glucose level; three times a day
MetforminDrug
| Study group | Role | What they receive |
|---|---|---|
| Exenatide (BET) | Experimental | Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) Receives: Drug: exenatide; Drug: Metformin; Drug: Insulin/ Glargine |
| Insulin Lispro (BBT) | Active comparator | Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) Receives: Drug: insulin lispro; Drug: Metformin; Drug: Insulin/ Glargine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30
Change in HbA1c from baseline following 30 weeks of therapy (i.e. HbA1c at week 30 minus HbA1c at baseline).
Measured: Baseline, 30 weeks
Secondary outcomes (12)
Percentage of Participants Achieving HbA1C < 7.0%
Percentage of participants achieving HbA1C < 7.0%
Measured: Week 30
Percent of Participants Achieving HbA1c ≤ 6.5%.
Percent of participants achieving HbA1c ≤ 6.5%.
Measured: Week 30
Change in Fasting Blood Glucose (FBG) From Baseline to Week 30.
Change in fasting blood glucose (FBG) from Baseline to Week 30 using MMRM model. The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.
Measured: Baseline, Week 30
Change in Total Cholesterol From Baseline to Week 30
Change in total cholesterol from baseline to Week 30 using ANCOVA model. The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.
Measured: Baseline, week 30
Change in High Density Lipoprotein (HDL) From Baseline to Week 30
Change in High Density Lipoprotein (HDL) from baseline to Week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.
Measured: Baseline, week 30
Change in Low Density Lipoprotein (LDL) From Baseline to Week 30
Change in Low Density Lipoprotein (LDL) from baseline to week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.
Measured: Baseline, Week 30
Change in Body Weight From Baseline to Week 30.
Change in body weight from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.
Measured: baseline, week 30
Change in Systolic Blood Pressure (SBP) From Baseline to Week 30
Change in Systolic Blood Pressure (SBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.
Measured: Baseline, Week 30
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 30
Change in Diastolic Blood Pressure (DBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.
Measured: baseline, Week 30
Daily Insulin Glargine Dose at Baseline and at Week 30
Daily Insulin Glargine Dose at baseline and at Week 30
Measured: Baseline, week 30
Major Hypoglycemia Rate Per Year
Mean (standard deviation) of major hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Major hypoglycemia was defined as any symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and requiring the assistance of another person because of severe impairment in consciousness or behavior.
Measured: 30 weeks
Minor Hypoglycemia Rate Per Year
Mean (standard deviation) of minor hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Minor hypoglycemia was defined as any time a participant feels that he or she is experiencing a sign or symptom associated with hypoglycemia that is either self-treated by the participant or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL)
Measured: 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2009 (estimated)
- Study startSep 2009
- Primary completionAug 2012
- Study completionAug 2012
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 (1)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
- 1,036 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, MD, Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00960661
- Sponsor's protocol ID
- H8O-EW-GWDM
- Status last verified
- Mar 2015
- First submitted
- 17 Aug 2009
- Last updated
- 7 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.
PubMed 25011946
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 Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Insulin Glargine With Either Metformin or Metformin and Sulfonylurea
- ClinicalTrials.gov ID
- NCT00960661
- Acronym / sponsor ID
- H8O-EW-GWDM
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- diabetes, exenatide, Byetta, insulin lispro, Humalog, insulin glargine, Lantus, Amylin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,036 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Study start
- Sep 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 18 Aug 2009 (estimated)
- Results
- Posted 17 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will compare two combination therapies: 1) Combined Basal Insulin Glargine (once a day), Exenatide (twice a day), and Metformin Therapy; or 2) Combined Basal Insulin Glargine (once a day), Bolus Insulin Lispro (three times a day), and Metformin Therapy, in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exenatide (BET) | Experimental | Drug: exenatide, Drug: Metformin, Drug: Insulin/ GlargineBasal Insulin/Glargine, Exenatide and Metformin Therapy (BET) |
| Insulin Lispro (BBT) | Active comparator | Drug: insulin lispro, Drug: Metformin, Drug: Insulin/ GlargineBasal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have been taking a basal insulin Glargine, at dose of ≥ 20 units/day, for at least 3 months prior to study start.
- Have been taking basal insulin Glargine at dose of ≥ 20 units/day, in combination with 1 of the following oral antidiabetic medication (OAM) regimens, for at least 3 months prior to study start:
- Have an HbA1C > 7.0% and ≤ 10.0%.
- Have a body mass index (BMI) between ≥ 25 and ≤ 45 kg/m2.
Key exclusion criteria (6 listed)
- Are currently taking OAM that is not described above and not allowed with concurrent use of insulin per local product label.
- Have taken more than 1 week within 1 month prior to the study start any glucose-lowering medications not included above either alone or in combination formulations, or have used a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phenylpropanolamine, rimonabant or similar over-the-counter medications).
- Have taken any insulin other than Glargine within the 3 months prior to study start for more than 1 week.
- Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, and inhaled preparations) within 4 weeks prior to the study start.
- Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
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, 5mcg (4 weeks) followed by 10mcg (26 weeks), twice a day | Drug | Exenatide (BET) |
| insulin lisproAlso: Humalogtitrated based on pre-meal glucose level; three times a day | Drug | Insulin Lispro (BBT) |
| Metformin | Drug | Exenatide (BET), Insulin Lispro (BBT) |
| Insulin/ Glargine | Drug | Exenatide (BET), Insulin Lispro (BBT) |
Primary outcome
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30
Time frame: Baseline, 30 weeks
Change in HbA1c from baseline following 30 weeks of therapy (i.e. HbA1c at week 30 minus HbA1c at baseline).
12 secondary outcomes
Percentage of Participants Achieving HbA1C < 7.0%
Time frame: Week 30
Percent of Participants Achieving HbA1c ≤ 6.5%.
Time frame: Week 30
Change in Fasting Blood Glucose (FBG) From Baseline to Week 30.
Time frame: Baseline, Week 30
Change in Total Cholesterol From Baseline to Week 30
Time frame: Baseline, week 30
Change in High Density Lipoprotein (HDL) From Baseline to Week 30
Time frame: Baseline, week 30
Change in Low Density Lipoprotein (LDL) From Baseline to Week 30
Time frame: Baseline, Week 30
Change in Body Weight From Baseline to Week 30.
Time frame: baseline, week 30
Change in Systolic Blood Pressure (SBP) From Baseline to Week 30
Time frame: Baseline, Week 30
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 30
Time frame: baseline, Week 30
Daily Insulin Glargine Dose at Baseline and at Week 30
Time frame: Baseline, week 30
Major Hypoglycemia Rate Per Year
Time frame: 30 weeks
Minor Hypoglycemia Rate Per Year
Time frame: 30 weeks
Results and safety
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 25011946Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.
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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.
Chief Medical Officer, MD study director
Eli Lilly and Company
95 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing exenatide, insulin lispro and Metformin in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 95 sites in 18 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 6 inclusion and 6 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 95 sites in France, Argentina, Germany, Netherlands, Sweden and 13 more countries. 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 17 Dec 2013). 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?
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30 (time frame: Baseline, 30 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 NCT00960661, which also lists 1 linked publication.
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; AzTrials last refreshed its copy on 7 Nov 2026.