Diabetes Mellitus, Type 2Phase 3NCT00798161

Safety and Efficacy of Linagliptin (BI 1356) Plus Metformin in Type 2 Diabetes, Factorial Design

A Phase 3 study testing BI 1356, BI 1356 + metformin and Metformin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 138 sites in 14 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

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: BI 1356, BI 1356 + metformin and Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 857 participants
Where: 138 sitesin 14 countries
Study dates: Dec 2008to May 2010
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 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with type 2 diabetes (drug naive or pre-treated) with insufficient glycaemic control (HbA1c higher or equal than 7.5 to less than 11.0 %), with very poor glycaemic control (HbA1c higher or equal than 11.0 %) who are not eligible for randomisation to be included in the open-label arm

Who cannot join

Myocardial infarction, stroke or transient ischemic attack (TIA), unstable or acute congestive heart failure, impaired hepatic function, treatment with rosiglitazone or pioglitazone, with a GLP1 analogue, with insulin, with anti-obesity drugs, with systemic steroids, renal failure or impairment, gastric bypass

Trial locations and contacts

138 sites in 14 countries.

Country

City, postcode or hospital

138 sites in 14 countries

France41 sites

1218.46.3303D Boehringer Ingelheim Investigational Site
Aire Sur l'Aadour
1218.46.3308B Boehringer Ingelheim Investigational Site
Bischheim
1218.46.3305A Boehringer Ingelheim Investigational Site
Bourges
1218.46.3304F Boehringer Ingelheim Investigational Site
Bousse
1218.46.3306D Boehringer Ingelheim Investigational Site
Carresse-Cassaber
1218.46.3308C Boehringer Ingelheim Investigational Site
Gambsheim
1218.46.3305D Boehringer Ingelheim Investigational Site
Garchizy
1218.46.3301A Boehringer Ingelheim Investigational Site
Grenoble Cédex
1218.46.3305B Boehringer Ingelheim Investigational Site
Guérigny
1218.46.3304A Boehringer Ingelheim Investigational Site
Jarny
1218.46.3302D Boehringer Ingelheim Investigational Site
La Riche
1218.46.3307A Boehringer Ingelheim Investigational Site
La Seyne-sur-Mer
1218.46.3307E Boehringer Ingelheim Investigational Site
La Seyne-sur-Mer
1218.46.3305G Boehringer Ingelheim Investigational Site
Lury-sur-Arnon
1218.46.3304D Boehringer Ingelheim Investigational Site
Mars-la-Tour
1218.46.3304B Boehringer Ingelheim Investigational Site
Mondelange
1218.46.3303A Boehringer Ingelheim Investigational Site
Mont-de-Marsan
1218.46.3303C Boehringer Ingelheim Investigational Site
Mont-de-Marsan
1218.46.3303E Boehringer Ingelheim Investigational Site
Mont-de-Marsan
1218.46.3304C Boehringer Ingelheim Investigational Site
Moûtiers
1218.46.3308F Boehringer Ingelheim Investigational Site
Mundolsheim
1218.46.3305C Boehringer Ingelheim Investigational Site
Nevers
1218.46.3305E Boehringer Ingelheim Investigational Site
Nevers
1218.46.3306A Boehringer Ingelheim Investigational Site
Orthez
1218.46.3306C Boehringer Ingelheim Investigational Site
Orthez
1218.46.3306E Boehringer Ingelheim Investigational Site
Orthez
1218.46.3306F Boehringer Ingelheim Investigational Site
Orthez
1218.46.3304E Boehringer Ingelheim Investigational Site
Pont-à-Mousson
1218.46.3302B Boehringer Ingelheim Investigational Site
Saint-Avertin
1218.46.3302C Boehringer Ingelheim Investigational Site
Saint-Avertin
1218.46.3303B Boehringer Ingelheim Investigational Site
Saint-Martin-d'Oney
1218.46.3306B Boehringer Ingelheim Investigational Site
Salies-de-Béarn
1218.46.3302E Boehringer Ingelheim Investigational Site
Savonnières
1218.46.3308A Boehringer Ingelheim Investigational Site
Strasbourg
1218.46.3308D Boehringer Ingelheim Investigational Site
Strasbourg
1218.46.3308E Boehringer Ingelheim Investigational Site
Strasbourg
1218.46.3307B Boehringer Ingelheim Investigational Site
Toulon
1218.46.3307C Boehringer Ingelheim Investigational Site
Toulon
1218.46.3307D Boehringer Ingelheim Investigational Site
Toulon
1218.46.3302A Boehringer Ingelheim Investigational Site
Tours
1218.46.3304H Boehringer Ingelheim Investigational Site
Vandœuvre-lès-Nancy

Other trials in France

India19 sites

1218.46.91007 Boehringer Ingelheim Investigational Site
Babgalore
1218.46.91001 Boehringer Ingelheim Investigational Site
Bangalore
1218.46.91004 Boehringer Ingelheim Investigational Site
Bangalore
1218.46.91012 Boehringer Ingelheim Investigational Site
Bangalore
1218.46.91011 Boehringer Ingelheim Investigational Site
Bhopal
1218.46.91003 Boehringer Ingelheim Investigational Site
Chennai
1218.46.91020 Boehringer Ingelheim Investigational Site
Chennai
1218.46.91009 Boehringer Ingelheim Investigational Site
Chhatrapati Sambhajinagar
1218.46.91018 Boehringer Ingelheim Investigational Site
Hyderadad
1218.46.91008 Boehringer Ingelheim Investigational Site
Jaipur
1218.46.91019 Boehringer Ingelheim Investigational Site
Madurai
1218.46.91013 Boehringer Ingelheim Investigational Site
Maharashtra
1218.46.91002 Boehringer Ingelheim Investigational Site
Manipal
1218.46.91015 Boehringer Ingelheim Investigational Site
Mumbai
1218.46.91014 Boehringer Ingelheim Investigational Site
Nagpur
1218.46.91017 Boehringer Ingelheim Investigational Site
New Delhi
1218.46.91016 Boehringer Ingelheim Investigational Site
P.O Trivandrum
1218.46.91010 Boehringer Ingelheim Investigational Site
Pune
1218.46.91006 Boehringer Ingelheim Investigational Site
West Bengal

Other trials in India

Netherlands13 sites

1218.46.31004 Boehringer Ingelheim Investigational Site
's-Hertogenbosch
1218.46.31005 Boehringer Ingelheim Investigational Site
's-Hertogenbosch
1218.46.31001 Boehringer Ingelheim Investigational Site
Almere Stad
1218.46.31008 Boehringer Ingelheim Investigational Site
Beek
1218.46.31002 Boehringer Ingelheim Investigational Site
Beek en Donk
1218.46.31010 Boehringer Ingelheim Investigational Site
Breda
1218.46.31011 Boehringer Ingelheim Investigational Site
Eindhoven
1218.46.31013 Boehringer Ingelheim Investigational Site
Groningen
1218.46.31012 Boehringer Ingelheim Investigational Site
Leiderdrop
1218.46.31016 Boehringer Ingelheim Investigational Site
Nijmegen
1218.46.31009 Boehringer Ingelheim Investigational Site
Rotterdam
1218.46.31014 Boehringer Ingelheim Investigational Site
Velp
1218.46.31015 Boehringer Ingelheim Investigational Site
Zoetermeer

Other trials in Netherlands

Canada9 sites

1218.46.11005 Boehringer Ingelheim Investigational Site
Calgary, Alberta
1218.46.11003 Boehringer Ingelheim Investigational Site
Edmonton, Alberta
1218.46.11004 Boehringer Ingelheim Investigational Site
Hamilton, Ontario
1218.46.11007 Boehringer Ingelheim Investigational Site
Oakville, Ontario
1218.46.11009 Boehringer Ingelheim Investigational Site
Oshawa, Ontario
1218.46.11002 Boehringer Ingelheim Investigational Site
Red Deer, Alberta
1218.46.11010 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1218.46.11006 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia
1218.46.11008 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba

Other trials in Canada

Mexico9 sites

1218.46.52006 Boehringer Ingelheim Investigational Site
Aguascalientes
1218.46.52002 Boehringer Ingelheim Investigational Site
Cuernavaca
1218.46.52003 Boehringer Ingelheim Investigational Site
Guadalajara
1218.46.52004 Boehringer Ingelheim Investigational Site
Guadalajara
1218.46.52007 Boehringer Ingelheim Investigational Site
México
1218.46.52008 Boehringer Ingelheim Investigational Site
México
1218.46.52001 Boehringer Ingelheim Investigational Site
Pachuca
1218.46.52010 Boehringer Ingelheim Investigational Site
Tijuana
1218.46.52009 Boehringer Ingelheim Investigational Site
Veracruz

Other trials in Mexico

Russia8 sites

1218.46.70001 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70002 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70003 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70004 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70006 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70008 Boehringer Ingelheim Investigational Site
Moscow
1218.46.70005 Boehringer Ingelheim Investigational Site
Saint Petersburg
1218.46.70007 Boehringer Ingelheim Investigational Site
Saint Petersburg

Other trials in Russia

Croatia6 sites

1218.46.38502 Boehringer Ingelheim Investigational Site
Karlovac
1218.46.38503 Boehringer Ingelheim Investigational Site
Krapinske Toplice
1218.46.38504 Boehringer Ingelheim Investigational Site
Osijek
1218.46.38505 Boehringer Ingelheim Investigational Site
Rijeka
1218.46.38501 Boehringer Ingelheim Investigational Site
Sisak
1218.46.38506 Boehringer Ingelheim Investigational Site
Zagreb

Other trials in Croatia

Germany6 sites

1218.46.49002 Boehringer Ingelheim Investigational Site
Bad Dürrheim-Sunthausen
1218.46.49001 Boehringer Ingelheim Investigational Site
Bad Mergentheim
1218.46.49006 Boehringer Ingelheim Investigational Site
Cologne
1218.46.49003 Boehringer Ingelheim Investigational Site
München
1218.46.49008 Boehringer Ingelheim Investigational Site
Neuwied
1218.46.49007 Boehringer Ingelheim Investigational Site
Schauenburg

Other trials in Germany

Ukraine6 sites

1218.46.38003 Boehringer Ingelheim Investigational Site
Kiev
1218.46.38001 Boehringer Ingelheim Investigational Site
Lviv
1218.46.38005 Boehringer Ingelheim Investigational Site
Lviv
1218.46.38002 Boehringer Ingelheim Investigational Site
Odesa
1218.46.38004 Boehringer Ingelheim Investigational Site
Odesa
1218.46.38006 Boehringer Ingelheim Investigational Site
Vinnitsa

Other trials in Ukraine

Romania5 sites

1218.46.40001 Boehringer Ingelheim Investigational Site
Alba Iulia
1218.46.40005 Boehringer Ingelheim Investigational Site
Galati
1218.46.40003 Boehringer Ingelheim Investigational Site
Oradea
1218.46.40002 Boehringer Ingelheim Investigational Site
Ploieşti
1218.46.40004 Boehringer Ingelheim Investigational Site
Satu Mare

Other trials in Romania

Sweden5 sites

1218.46.46002 Boehringer Ingelheim Investigational Site
Gothenburg
1218.46.46004 Boehringer Ingelheim Investigational Site
Gothenburg
1218.46.46003 Boehringer Ingelheim Investigational Site
Malmö
1218.46.46005 Boehringer Ingelheim Investigational Site
Stockholm
1218.46.46001 Boehringer Ingelheim Investigational Site
Uppsala

Other trials in Sweden

Tunisia5 sites

1218.46.2162A Boehringer Ingelheim Investigational Site
Bab Sâadoun Tunis
1218.46.2161A Boehringer Ingelheim Investigational Site
Tunis
1218.46.2161B Boehringer Ingelheim Investigational Site
Tunis
1218.46.2163A Boehringer Ingelheim Investigational Site
Tunis
1218.46.2163B Boehringer Ingelheim Investigational Site
Tunis

Other trials in Tunisia

Estonia3 sites

1218.46.37202 Boehringer Ingelheim Investigational Site
Pärnu
1218.46.37201 Boehringer Ingelheim Investigational Site
Tallinn
1218.46.37203 Boehringer Ingelheim Investigational Site
Tallinn

Other trials in Estonia

Lithuania3 sites

1218.46.37001 Boehringer Ingelheim Investigational Site
Kaunas
1218.46.37004 Boehringer Ingelheim Investigational Site
Kaunas
1218.46.37003 Boehringer Ingelheim Investigational Site
Vilnius

Other trials in Lithuania

About this study

Official title: A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Free Combination of BI 1356 2.5 mg + Metformin 500 mg, or of BI 1356 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg Twice Daily), and BI 1356 (5.0 mg Once Daily) Over 24 Weeks in Drug Naive or Previously Treated (4 Weeks Wash-out and 2 Weeks Placebo run-in) Type 2 Diabetic Patients With Insufficient Glycaemic Control

The objective of the randomised part of the study is to investigate the efficacy and safety of BI 1356 plus metformin compared to BI 1356 or metformin alone given for 24 weeks to drug naive or previously treated (4 weeks wash-out, 2 weeks placebo run-in) type 2 diabetic patients with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 1356 and metformin in type 2 diabetic patients with very poor glycaemic control for 24 weeks

Conditions: Diabetes Mellitus, Type 2
Being tested: BI 1356, BI 1356 + metformin, Metformin, matching placebo
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.

BI 1356Drug
BI 1356 high dose tablet, once daily
BI 1356 + metforminDrug
BI 1356 low dose tablet + Metformin 500 mg tablet, twice daily
Bi 1356 + metforminDrug
BI 1356 low dose tablet + Metformin 1000 mg tablet, twice daily
MetforminDrug
Metformin 500 mg tablet, twice daily
metforminDrug
metformin 1000 mg tablet, twice daily
matching placeboDrug
matching placebo

Study groups in NCT00798161
Study group	Role	What they receive
BI 1356 + metformin	Experimental	BI 1356 low dose + metformin 500 mg, twice daily Receives: Drug: BI 1356 + metformin
matching placebo	Placebo comparator	matching placebo Receives: Drug: matching placebo
BI 1356+ Metformin	Experimental	BI 1356 low dose + metformin 1000 mg, twice daily Receives: Drug: Bi 1356 + metformin
Metformin	Active comparator	Metformin 500 mg, twice daily Receives: Drug: Metformin
metformin	Active comparator	Metformin 1000 mg, twice daily Receives: Drug: metformin
BI 1356	Experimental	BI 1356 high dose, once daily Receives: Drug: BI 1356

What is being measured

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

HbA1c Change From Baseline at Week 24
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline and week 24

Secondary outcomes (17)

HbA1c Change From Baseline at Week 6
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline and week 6
HbA1c Change From Baseline at Week 12
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline and week 12
HbA1c Change From Baseline at Week 18
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Measured: Baseline and week 18
FPG Change From Baseline at Week 24
This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Measured: Baseline and week 24
FPG Change From Baseline at Week 2
This change from baseline reflects the Week 2 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Measured: Baseline and week 2
FPG Change From Baseline at Week 6
This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Measured: Baseline and week 6
FPG Change From Baseline at Week 12
This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Measured: Baseline and week 12
FPG Change From Baseline at Week 18
This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Measured: Baseline and week 18
Percentage of Patients With HbA1c <7.0% at Week 24
The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.
Measured: Baseline and Week 24
Percentage of Patients With HbA1c<7.0 at Week 24
The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.
Measured: Baseline and Week 24
Percentage of Patients With HbA1c <6.5% at Week 24
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%. Only patients with baseline HbA1c =< 6.5%
Measured: Baseline and Week 24
Percentage of Patients With HbA1c < 6.5% at Week 24
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%
Measured: Baseline and Week 24
Percentage of Patients With HbA1c Lowering by 0.5% at Week 24
The percentage of patients with an HbA1c reduction from baseline greater than 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%.
Measured: Baseline and week 24
Adjusted Means for 2h Post-Prandial Glucose (PPG) Change From Baseline at Week 24
This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline 2h PPG and previous anti-diabetic medication.
Measured: Baseline and week 24
HbA1c Change From Baseline at Week 24 for Open-label Patients
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percentage. Mean is unadjusted.
Measured: Baseline and week 24
FPG Change From Baseline at Week 24 for Open-label Patients
This change from baseline reflects the Week 24 FPG minus the baseline FPG. Mean is unadjusted.
Measured: Baseline and week 24
Use of Rescue Therapy
The use of rescue therapy (SUs, thiazolidinediones [TZDs], or insulin) was permitted only during the randomised treatment period of the trial (i.e. Visits 3 to 7), and was to be administered only if a patient had a 'confirmed' glucose level after an overnight fast.
Measured: 24 weeks

Timeline

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

Dec 2008May 2010

First posted25 Nov 2008 (estimated)
Study startDec 2008
Primary completionMay 2010

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 Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe 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: Double blind
Enrolment: 857 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00798161
Sponsor's protocol ID: 1218.46
Other IDs: 2008-001640-40, 2008
Status last verified: Dec 2013
First submitted: 24 Nov 2008
Last updated: 28 Jan 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Lv Q, Shen J, Miao L, Ye B, Schepers C, Plat A, Shi Y. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c </= 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials. Diabetes Ther. 2020 Jun;11(6):1317-1330. doi: 10.1007/s13300-020-00819-9. Epub 2020 Apr 23.
PubMed 32328953

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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Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Free Combination of BI 1356 2.5 mg + Metformin 500 mg, or of BI 1356 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg Twice Daily), and BI 1356 (5.0 mg Once Daily) Over 24 Weeks in Drug Naive or Previously Treated (4 Weeks Wash-out and 2 Weeks Placebo run-in) Type 2 Diabetic Patients With Insufficient Glycaemic Control
ClinicalTrials.gov ID: NCT00798161
Acronym / sponsor ID: 1218.46
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 857 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Dec 2008
Primary completion: May 2010 (actual)
First posted: 25 Nov 2008 (estimated)
Results: Posted 4 Aug 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: Double blind
Number of arms: 6

Arm	Type	Receives
BI 1356 + metformin	Experimental	Drug: BI 1356 + metforminBI 1356 low dose + metformin 500 mg, twice daily
matching placebo	Placebo comparator	Drug: matching placebomatching placebo
BI 1356+ Metformin	Experimental	Drug: Bi 1356 + metforminBI 1356 low dose + metformin 1000 mg, twice daily
Metformin	Active comparator	Drug: MetforminMetformin 500 mg, twice daily
metformin	Active comparator	Drug: metforminMetformin 1000 mg, twice daily
BI 1356	Experimental	Drug: BI 1356BI 1356 high dose, once daily

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Patients with type 2 diabetes (drug naive or pre-treated) with insufficient glycaemic control (HbA1c higher or equal than 7.5 to less than 11.0 %), with very poor glycaemic control (HbA1c higher or equal than 11.0 %) who are not eligible for randomisation to be included in the open-label arm

Key exclusion criteria (1 listed)

Myocardial infarction, stroke or transient ischemic attack (TIA), unstable or acute congestive heart failure, impaired hepatic function, treatment with rosiglitazone or pioglitazone, with a GLP1 analogue, with insulin, with anti-obesity drugs, with systemic steroids, renal failure or impairment, gastric bypass

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
BI 1356BI 1356 high dose tablet, once daily	Drug	BI 1356
BI 1356 + metforminBI 1356 low dose tablet + Metformin 500 mg tablet, twice daily	Drug	BI 1356 + metformin
Bi 1356 + metforminBI 1356 low dose tablet + Metformin 1000 mg tablet, twice daily	Drug	BI 1356+ Metformin
MetforminMetformin 500 mg tablet, twice daily	Drug	Metformin
metforminmetformin 1000 mg tablet, twice daily	Drug	metformin
matching placebomatching placebo	Drug	matching placebo

Primary outcome

HbA1c Change From Baseline at Week 24
Time frame: Baseline and week 24
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

17 secondary outcomes

HbA1c Change From Baseline at Week 6
Time frame: Baseline and week 6
HbA1c Change From Baseline at Week 12
Time frame: Baseline and week 12
HbA1c Change From Baseline at Week 18
Time frame: Baseline and week 18
FPG Change From Baseline at Week 24
Time frame: Baseline and week 24
FPG Change From Baseline at Week 2
Time frame: Baseline and week 2
FPG Change From Baseline at Week 6
Time frame: Baseline and week 6
FPG Change From Baseline at Week 12
Time frame: Baseline and week 12
FPG Change From Baseline at Week 18
Time frame: Baseline and week 18
Percentage of Patients With HbA1c <7.0% at Week 24
Time frame: Baseline and Week 24
Percentage of Patients With HbA1c<7.0 at Week 24
Time frame: Baseline and Week 24
Percentage of Patients With HbA1c <6.5% at Week 24
Time frame: Baseline and Week 24
Percentage of Patients With HbA1c < 6.5% at Week 24
Time frame: Baseline and Week 24
Percentage of Patients With HbA1c Lowering by 0.5% at Week 24
Time frame: Baseline and week 24
Adjusted Means for 2h Post-Prandial Glucose (PPG) Change From Baseline at Week 24
Time frame: Baseline and week 24
HbA1c Change From Baseline at Week 24 for Open-label Patients
Time frame: Baseline and week 24
FPG Change From Baseline at Week 24 for Open-label Patients
Time frame: Baseline and week 24
Use of Rescue Therapy
Time frame: 24 weeks

Results and safety

Results posted to the registry on 4 Aug 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
Placebo	72	54
M500 Twice Daily (BID)	144	127
M1000 BID	147	126
Lina 5	142	121
L2.5+M500 BID	143	127
L2.5 + M1000 BID	143	132
OL: L2.5+M1000 BID	66	56

Primary outcome: HbA1c Change From Baseline at Week 24

Time frame: Baseline and week 24. Mean (Standard Error). Unit: Percent

Measure	Placebo n = 65	M500BID n = 141	M1000BID n = 138	Lina5 n = 135	L2.5+M500BID n = 137	L2.5+M1000BID n = 140
Value	0.13 (0.11)	-0.64 (0.08)	-1.07 (0.08)	-0.45 (0.08)	-1.22 (0.08)	-1.59 (0.08)

M500BID vs L2.5+M500BID: Mean Difference (Final Values): -0.58 (95% CI -0.79 to -0.36), p <0.0001, ANCOVA
M1000BID vs L2.5+M1000BID: Median Difference (Final Values): -0.51 (95% CI -0.73 to -0.30), p <0.0001, ANCOVA
Lina5 vs L2.5+M500BID: Mean Difference (Final Values): -0.77 (95% CI -0.99 to -0.55), p <0.0001, ANCOVA

Population analysed: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

17 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day of first dose until day of last dose plus 7 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 72 (1.4%)	20 of 72 (27.8%)	Not reported
M500 BID	3 of 144 (2.1%)	27 of 144 (18.8%)	Not reported
M1000 BID	6 of 147 (4.1%)	27 of 147 (18.4%)	Not reported
Lina 5	3 of 142 (2.1%)	31 of 142 (21.8%)	Not reported
L2.5+M500 BID	2 of 143 (1.4%)	31 of 143 (21.7%)	Not reported
L2.5 + M1000 BID	2 of 143 (1.4%)	36 of 143 (25.2%)	Not reported
OL: L2.5+M1000 BID	1 of 66 (1.5%)	18 of 66 (27.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32328953Lv Q, Shen J, Miao L, Ye B, Schepers C, Plat A, Shi Y. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c </= 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials. Diabetes Ther. 2020 Jun;11(6):1317-1330. doi: 10.1007/s13300-020-00819-9. Epub 2020 Apr 23.

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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.

Boehringer Ingelheim study chair

Boehringer Ingelheim

138 sites in 14 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BI 1356, BI 1356 + metformin and Metformin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 138 sites in 14 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 1 inclusion and 1 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 28 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 138 sites in France, India, Netherlands, Canada, Mexico and 9 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. Some participants in this study may receive a placebo. 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 4 Aug 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?

HbA1c Change From Baseline at Week 24 (time frame: Baseline and week 24). 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 NCT00798161, 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 28 Jan 2014.