Type 2 DiabetesPhase 3NCT00660907

Efficacy and Safety of Dapagliflozin in Combination With Metformin in Type 2 Diabetes Patients

A Phase 3 study testing dapagliflozin, glipizide and metformin hydrochloride in people with Type 2 Diabetes, run by AstraZeneca at 76 sites in 10 countries.

Completed

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

Official record

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Trial summary

This study is being carried out to see if dapagliflozin as an addition to metformin is effective and safe in treating patients with type 2 diabetes when compared to glipizide (sulphonylurea) as an addition to metformin treatment. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Type 2 Diabetes
What is being tested?: dapagliflozin, glipizide and metformin hydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,217 participants
Where: 76 sitesin 10 countries
Study dates: Mar 2008to Jan 2013
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

Type 2 Diabetes
Treated with oral anti-diabetic drug therapy therapy including Metformin for at least 8 weeks prior to enrolment
HbA1c >6.5% and </=10%

Who cannot join

Type 1 Diabetes
Insulin therapy within one year of enrolment
Renal (kidney) failure or dysfunction

Trial locations and contacts

76 sites in 10 countries.

Country

City, postcode or hospital

76 sites in 10 countries

Germany12 sites

Research Site
Bad Lauterberg im Harz
Research Site
Berlin
Research Site
Dresden
Research Site
Essen
Research Site
Frankfurt
Research Site
Hamburg
Research Site
Heilbronn
Research Site
Ludwigshafen
Research Site
Mainz
Research Site
Pirna
Research Site
Schmiedeberg
Research Site
Wangen

Other trials in Germany

United Kingdom11 sites

Research Site
Addlestone
Research Site
Aylesbury
Research Site
Bath
Research Site
Bolton
Research Site
Bury Saint Edmonds
Research Site
Cookstown
Research Site
Coventry
Research Site
Ecclesfield
Research Site
Edinburgh
Research Site
Mortimer Reading
Research Site
Trowbridge

Other trials in United Kingdom

Netherlands10 sites

Research Site
Deurne
Research Site
Gorinchem
Research Site
Groningen
Research Site
Lichtenvoorde (gld)
Research Site
Losser
Research Site
Poortvliet
Research Site
Rotterdam
Research Site
The Hague
Research Site
Wildervank
Research Site
Zutphen

Other trials in Netherlands

Argentina9 sites

Research Site
Buenos Aires
Research Site
Caba
Research Site
Capital Federal
Research Site
Ciudad de Buenos Aires
Research Site
Córdoba
Research Site
Corrientes
Research Site
La Plata
Research Site
Rosario
Research Site
Santa Fe

Other trials in Argentina

Sweden8 sites

Research Site
Gothenburg
Research Site
Järfälla
Research Site
Lund
Research Site
Malmö
Research Site
Skene
Research Site
Södertälje
Research Site
Stockholm
Research Site
Umeå

Other trials in Sweden

South Africa7 sites

Research Site
Cape Town
Research Site
Durban
Research Site
eMkhomazi
Research Site
Johannesburg
Research Site
Parow
Research Site
Pretoria
Research Site
Witbank

Other trials in South Africa

France6 sites

Research Site
L'Aigle
Research Site
Mûrs-Erigné
Research Site
Nantes
Research Site
Paris
Research Site
Tours
Research Site
Vannes

Other trials in France

Spain6 sites

Research Site
Alicante
Research Site
Alzira (Valencia)
Research Site
Barcelona
Research Site
Cornellá de Llobregat (bcn)
Research Site
Madrid
Research Site
Seville

Other trials in Spain

Mexico4 sites

Research Site
Acapulco
Research Site
Guadalajara
Research Site
México
Research Site
Veracruz

Other trials in Mexico

Italy3 sites

Research Site
Perugia
Research Site
Pisa
Research Site
Roma

Other trials in Italy

About this study

Official title: A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 156-Week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.

Conditions: Type 2 Diabetes
Being tested: dapagliflozin, glipizide, metformin hydrochloride
Keywords: Dapagliflozin, efficacy, safety, metformin, Type 2 diabetes
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

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

dapagliflozinDrug
Tablet oral 2.5, 5, or 10 mg total daily dose once daily 208 weeks
glipizideDrug
Also called Glucotrol
Capsule oral 5, 10, or 20 mg total daily dose once or split/twice daily 208 weeks
metformin hydrochlorideDrug
Also called Glucophage
Tablet oral 1500, 2000, or 2500 mg total daily dose split/twice daily 218 weeks

Study groups in NCT00660907
Study group	Role	What they receive
1	Experimental	dapagliflozin plus metformin Receives: Drug: dapagliflozin; Drug: metformin hydrochloride
2	Active comparator	glipizide plus metformin Receives: Drug: glipizide; Drug: metformin hydrochloride

What is being measured

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

Adjusted Mean Change in HbA1c Levels
To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.
Measured: Baseline to Week 52

Secondary outcomes (3)

Adjusted Mean Change in Body Weight
To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight after 52 weeks double-blind treatment.
Measured: Baseline to Week 52
Proportion of Participants With at Least One Episode of Hypoglycemia
To assess the effect of dapagliflozin plus metformin treatment compared to glipizide plus metformin on the occurrence of hypoglycemic events. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value.
Measured: Baseline to Week 52
Proportion of Participants With Body Weight Reduction of at Least 5%
To evaluate the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight assessed by a reduction after 52 weeks of at least 5% compared to baseline. Least Squares Mean represents the percent of participants adjusted for baseline value.
Measured: Baseline to Week 52

Timeline

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

Mar 2008Jan 2013

First posted17 Apr 2008 (estimated)
Study startMar 2008
Primary completionDec 2009
Study completionJan 2013

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 (2)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies 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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,217 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00660907
Sponsor's protocol ID: D1690C00004
Status last verified: Mar 2015
First submitted: 15 Apr 2008
Last updated: 30 Mar 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011 Sep;34(9):2015-22. doi: 10.2337/dc11-0606. Epub 2011 Aug 4.
PubMed 21816980
Nauck M, del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ. [Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin]. Dtsch Med Wochenschr. 2013 Apr;138 Suppl 1:S6-15. doi: 10.1055/s-0032-1305283. Epub 2013 Mar 25. German.
PubMed 23529570

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?

See locations

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All Type 2 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 156-Week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.
ClinicalTrials.gov ID: NCT00660907
Acronym / sponsor ID: D1690C00004
Conditions: Type 2 Diabetes
Keywords: Dapagliflozin, efficacy, safety, metformin, Type 2 diabetes
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,217 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Bristol-Myers Squibb
Study start: Mar 2008
Primary completion: Dec 2009 (actual)
Study completion: Jan 2013 (actual)
First posted: 17 Apr 2008 (estimated)
Results: Posted 23 Aug 2013

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: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: dapagliflozin, Drug: metformin hydrochloridedapagliflozin plus metformin
2	Active comparator	Drug: glipizide, Drug: metformin hydrochlorideglipizide plus metformin

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Type 2 Diabetes
Treated with oral anti-diabetic drug therapy therapy including Metformin for at least 8 weeks prior to enrolment
HbA1c >6.5% and </=10%

Key exclusion criteria (3 listed)

Type 1 Diabetes
Insulin therapy within one year of enrolment
Renal (kidney) failure or dysfunction

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
dapagliflozinTablet oral 2.5, 5, or 10 mg total daily dose once daily 208 weeks	Drug	1
glipizideAlso: GlucotrolCapsule oral 5, 10, or 20 mg total daily dose once or split/twice daily 208 weeks	Drug	2
metformin hydrochlorideAlso: GlucophageTablet oral 1500, 2000, or 2500 mg total daily dose split/twice daily 218 weeks	Drug	1, 2

Primary outcome

Adjusted Mean Change in HbA1c Levels
Time frame: Baseline to Week 52
To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.

3 secondary outcomes

Adjusted Mean Change in Body Weight
Time frame: Baseline to Week 52
Proportion of Participants With at Least One Episode of Hypoglycemia
Time frame: Baseline to Week 52
Proportion of Participants With Body Weight Reduction of at Least 5%
Time frame: Baseline to Week 52

Results and safety

Results posted to the registry on 23 Aug 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dapagliflozin Plus Metformin	406	322
Glipizide Plus Metformin	408	314

Primary outcome: Adjusted Mean Change in HbA1c Levels

Time frame: Baseline to Week 52. Least squares mean (95% Confidence Interval). Unit: percent

Measure	Dapagliflozin Plus Metformin n = 400	Glipizide Plus Metformin n = 401
Value	-0.52 (-0.60 to -0.44)	-0.52 (-0.60 to -0.44)

Dapagliflozin Plus Metformin vs Glipizide Plus Metformin: Mean Difference (Final Values): 0.00 (95% CI -0.11 to 0.11), p <0.0001, ANCOVA

Population analysed: Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dapagliflozin Plus Metformin	35 of 406 (8.6%)	163 of 406 (40.1%)	Not reported
Glipizide Plus Metformin	46 of 408 (11.3%)	260 of 408 (63.7%)	Not reported

Limitations and caveats (from the sponsor): For participants who did not complete 52 weeks LOCF (last observation carried forward) was used.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21816980Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011 Sep;34(9):2015-22. doi: 10.2337/dc11-0606. Epub 2011 Aug 4.
Derived from this study: PubMed 23529570Nauck M, del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ. [Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin]. Dtsch Med Wochenschr. 2013 Apr;138 Suppl 1:S6-15. doi: 10.1055/s-0032-1305283. Epub 2013 Mar 25. German.
CSR-D1690C00004.pdfLink provided by the sponsor.

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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.

Michael A. Nauck, Prof. Dr. med. principal investigator

Diabeteszentrum Bad Lauterberg, Germany

76 sites in 10 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dapagliflozin, glipizide and metformin hydrochloride in people with Type 2 Diabetes, run by AstraZeneca at 76 sites in 10 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 3 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 30 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in Germany, United Kingdom, Netherlands, Argentina, Sweden and 5 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 23 Aug 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?

Adjusted Mean Change in HbA1c Levels (time frame: Baseline to Week 52). 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 NCT00660907, which also lists 2 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 30 Mar 2015.