Diabetes Mellitus, Type 2Phase 3NCT01708902

Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients

A Phase 3 study testing linagliptin2.5mg/metformin1000mg, linagliptin 5mg and Metformin 500mg in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 56 sites in 4 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

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: linagliptin2.5mg/metformin1000mg, linagliptin 5mg and Metformin 500mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 876 participants
Where: 56 sitesin 4 countries
Study dates: Oct 2012to Apr 2014
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

Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent
Male and female patients on diet and exercise regimen who are drug-naïve
Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/= 11.0 % for the additional parallel group
Age >/= 18 and </= 80 years at Visit 1a (Screening)
Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)
Signed and dated written informed consent by date of Visit 1a in accordance with good clinical practice(GCP) and local legislation

Who cannot join

Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
In main group, the patients with investigational medicinal product(IMP) compliance < 80 % or >120 % during 2 weeks placebo run in period
Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo
Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening

Show all 19Show fewer

Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
Concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing the consent form or during the trial.
Pre-menopausal women (last menstruation </= 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study
Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
Renal failure or renal impairment at Visit 1a (screening) with an Estimated Glomerular Filtration Rate(eGFR) < 60 ml/min
Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
Dehydration by clinical judgement of the investigator
Clinical detected unstable or acute congestive heart failure
Acute or chronic metabolic acidosis (present in patient history)
Hereditary galactose intolerance
Known history of pancreatitis and chronic pancreatitis
Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within last 5 years.
Any other clinical condition that would jeopardize patients safety while participating in this clinical trial at the discretion of investigator

Trial locations and contacts

56 sites in 4 countries.

Country

City, postcode or hospital

56 sites in 4 countries

China38 sites

1288.18.86001 Boehringer Ingelheim Investigational Site
Beijing
1288.18.86002 Boehringer Ingelheim Investigational Site
Beijing
1288.18.86003 Boehringer Ingelheim Investigational Site
Beijing
1288.18.86004 Boehringer Ingelheim Investigational Site
Beijing
1288.18.86046 Boehringer Ingelheim Investigational Site
Beijing
1288.18.86019 Boehringer Ingelheim Investigational Site
Changchun
1288.18.86020 Boehringer Ingelheim Investigational Site
Changchun
1288.18.86028 Boehringer Ingelheim Investigational Site
Changsha
1288.18.86029 Boehringer Ingelheim Investigational Site
Changsha
1288.18.86050 Boehringer Ingelheim Investigational Site
Changsha
1288.18.86045 Boehringer Ingelheim Investigational Site
Chengdu
1288.18.86042 Boehringer Ingelheim Investigational Site
Chongqing
1288.18.86023 Boehringer Ingelheim Investigational Site
Dalian
1288.18.86009 Boehringer Ingelheim Investigational Site
Guangzhou
1288.18.86010 Boehringer Ingelheim Investigational Site
Guangzhou
1288.18.86012 Boehringer Ingelheim Investigational Site
Guangzhou
1288.18.86047 Boehringer Ingelheim Investigational Site
Haerbin
1288.18.86032 Boehringer Ingelheim Investigational Site
Hefei
1288.18.86016 Boehringer Ingelheim Investigational Site
Hengshui
1288.18.86017 Boehringer Ingelheim Investigational Site
Jinan
1288.18.86026 Boehringer Ingelheim Investigational Site
Lanzhou
1288.18.86039 Boehringer Ingelheim Investigational Site
Nanchang
1288.18.86035 Boehringer Ingelheim Investigational Site
Nanjing
1288.18.86036 Boehringer Ingelheim Investigational Site
Nanjing
1288.18.86034 Boehringer Ingelheim Investigational Site
Nanning
1288.18.86006 Boehringer Ingelheim Investigational Site
Shanghai
1288.18.86007 Boehringer Ingelheim Investigational Site
Shanghai
1288.18.86008 Boehringer Ingelheim Investigational Site
Shanghai
1288.18.86013 Boehringer Ingelheim Investigational Site
Shantou
1288.18.86022 Boehringer Ingelheim Investigational Site
Shenyang
1288.18.86014 Boehringer Ingelheim Investigational Site
Shijiazhuang
1288.18.86015 Boehringer Ingelheim Investigational Site
Shijiazhuang
1288.18.86038 Boehringer Ingelheim Investigational Site
Suzhou
1288.18.86049 Boehringer Ingelheim Investigational Site
Wuhan
1288.18.86033 Boehringer Ingelheim Investigational Site
Wuhu
1288.18.86024 Boehringer Ingelheim Investigational Site
Xi'an
1288.18.86025 Boehringer Ingelheim Investigational Site
Xi'an
1288.18.86030 Boehringer Ingelheim Investigational Site
Yueyang

Other trials in China

Malaysia8 sites

1288.18.60004 Boehringer Ingelheim Investigational Site
Kelantan
1288.18.60003 Boehringer Ingelheim Investigational Site
Kuala Selangor
1288.18.60002 Boehringer Ingelheim Investigational Site
Malacca
1288.18.60005 Boehringer Ingelheim Investigational Site
Negeri Sembilan
1288.18.60007 Boehringer Ingelheim Investigational Site
Negeri Sembilan
1288.18.60001 Boehringer Ingelheim Investigational Site
Perak
1288.18.60006 Boehringer Ingelheim Investigational Site
Perak
1288.18.60008 Boehringer Ingelheim Investigational Site
Putrajaya

Other trials in Malaysia

Philippines7 sites

1288.18.63007 Boehringer Ingelheim Investigational Site
Cebu
1288.18.63003 Boehringer Ingelheim Investigational Site
Cebu City
1288.18.63002 Boehringer Ingelheim Investigational Site
Makati City
1288.18.63001 Boehringer Ingelheim Investigational Site
Manila
1288.18.63008 Boehringer Ingelheim Investigational Site
Quezon City
1288.18.63006 Boehringer Ingelheim Investigational Site
Surigao City
1288.18.63005 Boehringer Ingelheim Investigational Site
Tagum

Other trials in Philippines

Vietnam3 sites

1288.18.84003 Boehringer Ingelheim Investigational Site
Hanoi
1288.18.84001 Boehringer Ingelheim Investigational Site
Ho Chi Minh City
1288.18.84002 Boehringer Ingelheim Investigational Site
Ho Chi Minh City

Other trials in Vietnam

About this study

Official title: A Phase III Randomised, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Fix Dose Combination of Linagliptin 2.5 mg + Metformin 500 mg, or of Linagliptin 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg, Twice Daily), and Linagliptin (5.0 mg, Once Daily) Over 24 Weeks in Treatment naïve Type 2 Diabetic Patients With Insufficient Glycaemic Control

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients

Conditions: Diabetes Mellitus, Type 2
Being tested: linagliptin2.5mg/metformin1000mg, linagliptin 5mg, Metformin 500mg, linagliptin2.5mg/metformin500mg, Metformin 1000mg
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.

linagliptin2.5mg/metformin1000mgDrug
linagliptin2.5mg/metformin1000mg BID
linagliptin2.5mg/metformin1000mgDrug
linagliptin2.5mg/metformin1000mg BID
linagliptin 5mgDrug
linagliptin 5mg once daily
Metformin 500mgDrug
Metformin 500mg BID
linagliptin2.5mg/metformin500mgDrug
linagliptin2.5mg/metformin500mg BID
linagliptin2.5mg/metformin500mgDrug
linagliptin2.5mg/metformin500mg BID
linagliptin 5mgDrug
linagliptin 5mg once daily
Metformin 1000mgDrug
Metformin 1000mg BID

Study groups in NCT01708902
Study group	Role	What they receive
linagliptin2.5mg / metformin500mg BID	Experimental	patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID Receives: Drug: linagliptin 5mg; Drug: Metformin 500mg
linagliptin2.5mg / metformin1000mg BID	Experimental	patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID Receives: Drug: linagliptin 5mg; Drug: Metformin 1000mg
metformin 500mg BID	Active comparator	patient to receive a tablet containing metformin 500mg BID Receives: Drug: linagliptin2.5mg/metformin500mg
metformin 1000mg BID	Active comparator	patient to receive a tablet containing metformin 1000mg BID Receives: Drug: linagliptin2.5mg/metformin1000mg
linagliptin 5 mg QD	Active comparator	patient to receive a tablet containing linagliptin 5mg once daily Receives: Drug: linagliptin2.5mg/metformin1000mg; Drug: linagliptin2.5mg/metformin500mg

What is being measured

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

The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group
The change from baseline in HbA1c after 24 weeks of treatment in main group.
The mean was adjusted by baseline HbA1c and treatment group.
Measured: Baseline and week 24
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)
The change from baseline in HbA1c after 24 weeks of treatment in main group. Only subjects from the FAS with measured HbA1c values (observed cases [OC]) were considered.
The mean was adjusted by treatment, baseline HbA1c, week and treatment*week.
The sensitivity analysis was added as the primary analysis failed with borderline results.
Measured: Baseline and week 24
The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG
The change from baseline in HbA1c after 12 weeks of treatment in additional parallel group (APG)
The mean was adjusted by baseline HbA1c and treatment group.
Measured: Baseline and week 12

Secondary outcomes (10)

The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 24 weeks of treatment in main group.
Measured: Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG
The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % after 12 weeks of treatment in APG.
Measured: Week 12 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 24 weeks of treatment in main group.
Measured: Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG
The occurrence of treat to target efficacy response in terms of HbA1c < 6.5% after 12 weeks of treatment in APG.
Measured: Week 12 (after first drug administration)
The Occurrence of Relative Efficacy Response in Main Group
The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) in main group
Measured: From baseline until week 24
The Occurrence of Relative Efficacy Response in APG
The Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 12 Weeks of Treatment) in APG
Measured: From baseline until week 12
The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group
The change in fasting plasma glucose (FPG) from baseline after 24 weeks of treatment in main group.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
Measured: Baseline and week 24
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG.
Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.
Measured: Baseline and week 12
The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group
The frequency of patients with use of rescue therapy during 24 week treatment period in main group.
For this analysis the main group contrast 'Metformin 1000mg BID, Linagliptin 2.5mg / Metformin 1000mg BID' could not be analysed due to lack of events in the Metformin 1000mg BID group.
Measured: From baseline until week 24
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG.
Measured: From baseline until week 12

Timeline

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

Oct 2012Apr 2014

First posted17 Oct 2012 (estimated)
Study startOct 2012
Primary completionApr 2014
Study completionApr 2014

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: Factorial
Masking: Double blind
Enrolment: 876 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01708902
Sponsor's protocol ID: 1288.18
Status last verified: Apr 2015
First submitted: 16 Oct 2012
Last updated: 24 Apr 2015
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 24 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Randomised, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Fix Dose Combination of Linagliptin 2.5 mg + Metformin 500 mg, or of Linagliptin 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg, Twice Daily), and Linagliptin (5.0 mg, Once Daily) Over 24 Weeks in Treatment naïve Type 2 Diabetic Patients With Insufficient Glycaemic Control
ClinicalTrials.gov ID: NCT01708902
Acronym / sponsor ID: 1288.18
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 876 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Oct 2012
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 17 Oct 2012 (estimated)
Results: Posted 24 Apr 2015

Clinical summary

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

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Double blind
Number of arms: 5

Arm	Type	Receives
linagliptin2.5mg / metformin500mg BID	Experimental	Drug: linagliptin 5mg, Drug: Metformin 500mgpatient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID
linagliptin2.5mg / metformin1000mg BID	Experimental	Drug: linagliptin 5mg, Drug: Metformin 1000mgpatient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID
metformin 500mg BID	Active comparator	Drug: linagliptin2.5mg/metformin500mgpatient to receive a tablet containing metformin 500mg BID
metformin 1000mg BID	Active comparator	Drug: linagliptin2.5mg/metformin1000mgpatient to receive a tablet containing metformin 1000mg BID
linagliptin 5 mg QD	Active comparator	Drug: linagliptin2.5mg/metformin1000mg, Drug: linagliptin2.5mg/metformin500mgpatient to receive a tablet containing linagliptin 5mg once daily

Who may qualify

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

Key inclusion criteria (6 listed)

Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent
Male and female patients on diet and exercise regimen who are drug-naïve
Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/= 11.0 % for the additional parallel group
Age >/= 18 and </= 80 years at Visit 1a (Screening)
Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)

Key exclusion criteria (19 listed)

Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
In main group, the patients with investigational medicinal product(IMP) compliance < 80 % or >120 % during 2 weeks placebo run in period
Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo

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
linagliptin2.5mg/metformin1000mglinagliptin2.5mg/metformin1000mg BID	Drug	metformin 1000mg BID
linagliptin2.5mg/metformin1000mglinagliptin2.5mg/metformin1000mg BID	Drug	linagliptin 5 mg QD
linagliptin 5mglinagliptin 5mg once daily	Drug	linagliptin2.5mg / metformin500mg BID
Metformin 500mgMetformin 500mg BID	Drug	linagliptin2.5mg / metformin500mg BID
linagliptin2.5mg/metformin500mglinagliptin2.5mg/metformin500mg BID	Drug	metformin 500mg BID
linagliptin2.5mg/metformin500mglinagliptin2.5mg/metformin500mg BID	Drug	linagliptin 5 mg QD
linagliptin 5mglinagliptin 5mg once daily	Drug	linagliptin2.5mg / metformin1000mg BID
Metformin 1000mgMetformin 1000mg BID	Drug	linagliptin2.5mg / metformin1000mg BID

Primary outcome

The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group
Time frame: Baseline and week 24
The change from baseline in HbA1c after 24 weeks of treatment in main group. The mean was adjusted by baseline HbA1c and treatment group.
The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)
Time frame: Baseline and week 24
The change from baseline in HbA1c after 24 weeks of treatment in main group. Only subjects from the FAS with measured HbA1c values (observed cases [OC]) were considered. The mean was adjusted by treatment, baseline HbA1c, week and treatment*week. The sensitivity analysis was added as the primary analysis failed with borderline results.
The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG
Time frame: Baseline and week 12
The change from baseline in HbA1c after 12 weeks of treatment in additional parallel group (APG) The mean was adjusted by baseline HbA1c and treatment group.

10 secondary outcomes

The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group
Time frame: Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG
Time frame: Week 12 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group
Time frame: Week 24 (after first drug administration)
The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG
Time frame: Week 12 (after first drug administration)
The Occurrence of Relative Efficacy Response in Main Group
Time frame: From baseline until week 24
The Occurrence of Relative Efficacy Response in APG
Time frame: From baseline until week 12
The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group
Time frame: Baseline and week 24
The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG
Time frame: Baseline and week 12
The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group
Time frame: From baseline until week 24
The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG
Time frame: From baseline until week 12

Results and safety

Results posted to the registry on 24 Apr 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Main: Linagliptin 5mg QD	147	130
Main: Metformin 500mg BID	145	137
Main: Metformin 1000mg BID	144	127
Main: Linagliptin 2.5mg / Metformin 500mg BID	147	137
Main: Linagliptin 2.5mg / Metformin 1000mg BID	147	131
APG: Linagliptin 5mg QD	71	64
APG: Linagliptin 2.5mg / Metformin 1000mg BID	72	65

Primary outcome: The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group

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

Measure	Main: Linagliptin 5mg QD n = 141	Main: Metformin 500mg BID n = 144	Main: Metformin 1000mg BID n = 133	Main: Linagliptin 2.5mg / Metformin 500mg BID n = 142	Main: Linagliptin 2.5mg / Metformin 1000mg BID n = 141
Value	-1.29 (0.08)	-1.64 (0.08)	-2.07 (0.08)	-2.15 (0.08)	-2.29 (0.08)

Main: Metformin 1000mg BID vs Main: Linagliptin 2.5mg / Metformin 1000mg BID: Mean Difference (Final Values): -0.22 (95% CI -0.45 to 0.01), p = 0.0587, ANCOVA
Main: Linagliptin 5mg QD vs Main: Linagliptin 2.5mg / Metformin 1000mg BID: Mean Difference (Final Values): -1.00 (95% CI -1.23 to -0.78), p <0.0001, ANCOVA
Main: Metformin 500mg BID vs Main: Linagliptin 2.5mg / Metformin 500mg BID: Mean Difference (Final Values): -0.51 (95% CI -0.73 to -0.29), p <0.0001, ANCOVA

Population analysed: Full analysis set (FAS): all randomised and treated patients who had a baseline and at least 1 on-treatment HbA1c value As the imputation rule for missing data the last observation carried forward (LOCF) was used.

Primary outcome: The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)

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

Measure	Main: Linagliptin 5mg QD n = 125	Main: Metformin 500mg BID n = 133	Main: Metformin 1000mg BID n = 127	Main: Linagliptin 2.5mg / Metformin 500mg BID n = 135	Main: Linagliptin 2.5mg / Metformin 1000mg BID n = 128
Value	-1.34 (0.08)	-1.68 (0.08)	-2.08 (0.08)	-2.16 (0.08)	-2.38 (0.08)

Main: Metformin 1000mg BID vs Main: Linagliptin 2.5mg / Metformin 1000mg BID: Mean Difference (Final Values): -0.30 (95% CI -0.53 to -0.07), p = 0.0109, ANCOVA
Main: Linagliptin 5mg QD vs Main: Linagliptin 2.5mg / Metformin 1000mg BID: Mean Difference (Final Values): -1.04 (95% CI -1.27 to -0.81), p <0.0001, ANCOVA
Main: Metformin 500mg BID vs Main: Linagliptin 2.5mg / Metformin 500mg BID: Mean Difference (Final Values): -0.47 (95% CI -0.70 to -0.24), p <0.0001, ANCOVA

Population analysed: FAS (OC): subjects from the FAS with measured HbA1c values (observed cases \[OC\]) were considered

Primary outcome: The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG

Time frame: Baseline and week 12. Mean (Standard Error). Unit: percentage

Measure	APG: Linagliptin 5mg QD n = 70	APG: Linagliptin 2.5mg / Metformin 1000mg BID n = 68
Value	-3.46 (0.22)	-4.71 (0.22)

APG: Linagliptin 5mg QD vs APG: Linagliptin 2.5mg / Metformin 1000mg BID: Mean Difference (Final Values): -1.25 (95% CI -1.87 to -0.63), p = 0.0001, ANCOVA

Population analysed: FAS (LOCF)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first drug administration (week 1) until end of treatment, up to 24 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Main: Linagliptin 5mg QD	2 of 147 (1.4%)	30 of 147 (20.4%)	Not reported
Main: Metformin 500mg BID	1 of 145 (0.7%)	31 of 145 (21.4%)	Not reported
Main: Metformin 1000mg BID	2 of 144 (1.4%)	42 of 144 (29.2%)	Not reported
Main: Linagliptin 2.5mg / Metformin 500mg BID	1 of 147 (0.7%)	32 of 147 (21.8%)	Not reported
Main: Linagliptin 2.5mg / Metformin 1000mg BID	4 of 147 (2.7%)	41 of 147 (27.9%)	Not reported
APG: Linagliptin 5mg QD up to Week 12	1 of 71 (1.4%)	20 of 71 (28.2%)	Not reported
APG: Linagliptin 2.5mg / Metformin 1000mg BID up to Week 12	1 of 72 (1.4%)	15 of 72 (20.8%)	Not reported
APG: Linagliptin 5mg After Week 12	0 of 33 (0%)	2 of 33 (6.1%)	Not reported
APG: Linagliptin 5mg - Linagliptin 2.5mg / Met After Week 12	1 of 31 (3.2%)	9 of 31 (29%)	Not reported
APG: Linagliptin 2.5mg / Metformin 1000mg After Week 12	1 of 65 (1.5%)	9 of 65 (13.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2015.
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.
Related InfoLink 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.

Boehringer Ingelheim study chair

Boehringer Ingelheim

56 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing linagliptin2.5mg/metformin1000mg, linagliptin 5mg and Metformin 500mg in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 56 sites in 4 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 19 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 24 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 56 sites in China, Malaysia, Philippines, Vietnam. 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 24 Apr 2015). 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?

The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group (time frame: Baseline and week 24). The study lists 3 primary outcomes in all. 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 NCT01708902, 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 24 Apr 2015.