Diabetes Mellitus, Type 2Phase 4NCT01438814

Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

A Phase 4 study testing metformin and linagliptin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 90 sites in 14 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

The aim of this study is to investigate the impact of the combination therapy of linagliptin and metformin at submaximal doses in reduction of Glycosylated haemoglobin (HbA1c) and metformin pre-specified gastro-intestinal (GI) side effects in treatment naive patients of with type 2 diabetes mellitus. 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?: metformin and linagliptin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 689 participants
Where: 90 sitesin 14 countries
Study dates: Nov 2011to Mar 2013
Phase: Phase 4
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 naive, defined as absence of any oral antidiabetic therapy or insulin for 12 weeks prior to randomization
Glycosylated haemoglobin A1c (HbA1c) >/= 7.0% (53 mmol/mol) to </= 10.0% (86 mmol/mol) at visit 1 (screening);
Age>/=18 and </=80 years at visit 1(screening);
Body Mass Index (BMI)</= 45kg/m2 at visit 1 (screening);
Signed and dated written informed consent by date of visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Who cannot join

Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (13.3mmol/L) after an overnight fast during screening/placebo run-in and confirmed by a second measurement (Not on the same day);
Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization
Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or Transient ischemia attack (TIA) within 3 months prior to informed consent;
Indication of liver disease/Impaired hepatic function, defined by serum levels of either Aspartate aminotransferase (ALT or SGPT), alanine aminotransferase (AST or SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at visit 1 and/or run-in phase,
Impaired renal function, defined as eGFR< 60ml/min (moderate or severe renal impairment, modification of diet in renal disease (MDRD) formula) as determined during screening or at run-in phase
Bariatric surgery within the past two years and other gastrointestinal surgeries that induced chronic malabsorption

Show all 18Show fewer

Medical history of Cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
Blood dyscrasia or any other disorders causing haemolysis or unstable Red Blood Cell (eg. malaria, babesiosis, haemolytic anemia)
Known history of pancreatitis and chronic pancreatitis
Contraindications to metformin according to the local label
Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen etc) leading to unstable body weight
Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM
Pre-menopausal women (last menstruation less than 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 and do not agree to submit to periodic pregnancy testing during participation in the trial or who do not agree to continue contraception for at least 30 days after the last dose of study drug. Acceptable methods of birth control include tubal ligation, transdermal patch, intra-uterine devices/systems(IUDs/IUSs), oral, implantable, or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomized partner.
Alcohol or drug abuse within 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
Participation in another trial with application of any investigational drug within 30 days prior to informed consent
Any other clinical condition that would jeopardize patients safety while participating in this trial

Trial locations and contacts

90 sites in 14 countries.

Country

City, postcode or hospital

90 sites in 14 countries

Canada15 sites

1218.60.20003 Boehringer Ingelheim Investigational Site
Burnaby, British Columbia
1218.60.20009 Boehringer Ingelheim Investigational Site
Calgary, Alberta
1218.60.20014 Boehringer Ingelheim Investigational Site
Coquitlam, British Columbia
1218.60.20012 Boehringer Ingelheim Investigational Site
Corunna, Ontario
1218.60.20004 Boehringer Ingelheim Investigational Site
Halifax, Nova Scotia
1218.60.20015 Boehringer Ingelheim Investigational Site
Hamilton, Ontario
1218.60.20006 Boehringer Ingelheim Investigational Site
London, Ontario
1218.60.20013 Boehringer Ingelheim Investigational Site
London, Ontario
1218.60.20001 Boehringer Ingelheim Investigational Site
Saint Romuald, Quebec
1218.60.20002 Boehringer Ingelheim Investigational Site
Sarnia, Ontario
1218.60.20011 Boehringer Ingelheim Investigational Site
Sarnia, Ontario
1218.60.20005 Boehringer Ingelheim Investigational Site
Strathroy, Ontario
1218.60.20010 Boehringer Ingelheim Investigational Site
Surrey, British Columbia
1218.60.20007 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1218.60.20016 Boehringer Ingelheim Investigational Site
Toronto, Ontario

Other trials in Canada

China12 sites

1218.60.86001 Boehringer Ingelheim Investigational Site
Beijing
1218.60.86003 Boehringer Ingelheim Investigational Site
Beijing
1218.60.86011 Boehringer Ingelheim Investigational Site
Changsha
1218.60.86012 Boehringer Ingelheim Investigational Site
Chengdu
1218.60.86010 Boehringer Ingelheim Investigational Site
Chongqing
1218.60.86013 Boehringer Ingelheim Investigational Site
Hubei
1218.60.86014 Boehringer Ingelheim Investigational Site
Hubei
1218.60.86006 Boehringer Ingelheim Investigational Site
Nanjing
1218.60.86007 Boehringer Ingelheim Investigational Site
Nanjing
1218.60.86005 Boehringer Ingelheim Investigational Site
Shanghai
1218.60.86009 Boehringer Ingelheim Investigational Site
Shenyang
1218.60.86008 Boehringer Ingelheim Investigational Site
Wuxi

Other trials in China

Spain10 sites

1218.60.34001 Boehringer Ingelheim Investigational Site
Barcelona
1218.60.34002 Boehringer Ingelheim Investigational Site
Barcelona
1218.60.34003 Boehringer Ingelheim Investigational Site
Barcelona
1218.60.34004 Boehringer Ingelheim Investigational Site
Barcelona
1218.60.34006 Boehringer Ingelheim Investigational Site
Borges Del Camp- Tarragona
1218.60.34005 Boehringer Ingelheim Investigational Site
Centelles
1218.60.34009 Boehringer Ingelheim Investigational Site
Granada
1218.60.34008 Boehringer Ingelheim Investigational Site
L'Hospitalet de Llobregat
1218.60.34007 Boehringer Ingelheim Investigational Site
Mataró
1218.60.34010 Boehringer Ingelheim Investigational Site
Valencia

Other trials in Spain

Germany8 sites

1218.60.49007 Boehringer Ingelheim Investigational Site
Berlin
1218.60.49008 Boehringer Ingelheim Investigational Site
Berlin
1218.60.49005 Boehringer Ingelheim Investigational Site
Dresden
1218.60.49004 Boehringer Ingelheim Investigational Site
Erfurt
1218.60.49006 Boehringer Ingelheim Investigational Site
Frankfurt
1218.60.49003 Boehringer Ingelheim Investigational Site
Hamburg
1218.60.49002 Boehringer Ingelheim Investigational Site
Neuwied
1218.60.49001 Boehringer Ingelheim Investigational Site
Unterschneidheim

Other trials in Germany

India8 sites

1218.60.91010 Boehringer Ingelheim Investigational Site
Bangalore
1218.60.91004 Boehringer Ingelheim Investigational Site
Chhatrapati Sambhajinagar
1218.60.91005 Boehringer Ingelheim Investigational Site
Coimbatore
1218.60.91008 Boehringer Ingelheim Investigational Site
Kolkata
1218.60.91001 Boehringer Ingelheim Investigational Site
Nagpur
1218.60.91007 Boehringer Ingelheim Investigational Site
Nagpur
1218.60.91003 Boehringer Ingelheim Investigational Site
Pune
1218.60.91006 Boehringer Ingelheim Investigational Site
Pune

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Taiwan6 sites

1218.60.88006 Boehringer Ingelheim Investigational Site
Chiayi County
1218.60.88003 Boehringer Ingelheim Investigational Site
Kaohsiung City
1218.60.88001 Boehringer Ingelheim Investigational Site
Taichung
1218.60.88007 Boehringer Ingelheim Investigational Site
Taichung
1218.60.88002 Boehringer Ingelheim Investigational Site
Tainan
1218.60.88004 Boehringer Ingelheim Investigational Site
Taipei County

Other trials in Taiwan

Belgium5 sites

1218.60.32001 Boehringer Ingelheim Investigational Site
Genk
1218.60.32005 Boehringer Ingelheim Investigational Site
Ham
1218.60.32002 Boehringer Ingelheim Investigational Site
Hasselt
1218.60.32004 Boehringer Ingelheim Investigational Site
Natoye
1218.60.32003 Boehringer Ingelheim Investigational Site
Tremelo

Other trials in Belgium

Lebanon5 sites

1218.60.96001 Boehringer Ingelheim Investigational Site
Beirut
1218.60.96002 Boehringer Ingelheim Investigational Site
Beirut
1218.60.96004 Boehringer Ingelheim Investigational Site
Byblos
1218.60.96003 Boehringer Ingelheim Investigational Site
Hazmiyeh
1218.60.96005 Boehringer Ingelheim Investigational Site
Saida

Other trials in Lebanon

Mexico5 sites

1218.60.52005 Boehringer Ingelheim Investigational Site
Aguascalientes
1218.60.52003 Boehringer Ingelheim Investigational Site
Cuernavaca
1218.60.52001 Boehringer Ingelheim Investigational Site
Durango
1218.60.52002 Boehringer Ingelheim Investigational Site
Durango
1218.60.52004 Boehringer Ingelheim Investigational Site
Monterrey

Other trials in Mexico

Philippines5 sites

1218.60.63001 Boehringer Ingelheim Investigational Site
Cebu City, Philippines
1218.60.63004 Boehringer Ingelheim Investigational Site
Iloilo City, Philippines
1218.60.63003 Boehringer Ingelheim Investigational Site
Manila
1218.60.63002 Boehringer Ingelheim Investigational Site
Marikina City, Philippines
1218.60.63005 Boehringer Ingelheim Investigational Site
Quezon City

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Bangladesh3 sites

1218.60.90001 Boehringer Ingelheim Investigational Site
Dhaka
1218.60.90002 Boehringer Ingelheim Investigational Site
Dhaka
1218.60.90003 Boehringer Ingelheim Investigational Site
Dhaka

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Guatemala3 sites

1218.60.50001 Boehringer Ingelheim Investigational Site
Guatemala City
1218.60.50002 Boehringer Ingelheim Investigational Site
Guatemala City
1218.60.50003 Boehringer Ingelheim Investigational Site
Guatemala City

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Peru3 sites

1218.60.51001 Boehringer Ingelheim Investigational Site
Lima
1218.60.51002 Boehringer Ingelheim Investigational Site
Lima
1218.60.51004 Boehringer Ingelheim Investigational Site
Piura

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Hong Kong2 sites

1218.60.85001 Boehringer Ingelheim Investigational Site
Hong Kong
1218.60.85002 Boehringer Ingelheim Investigational Site
Hong Kong

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About this study

Official title: A Randomised, Double-blind, Double-dummy, Active-comparator Controlled Study Investigating the Efficacy and Safety of Linagliptin Co-administered With Metformin QD at Evening Time Versus Metformin BID Over 14 Weeks in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

Conditions: Diabetes Mellitus, Type 2
Being tested: metformin placebo, linagliptin placebo, metformin, linagliptin
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.

metformin placeboDrug
metformin placebo tablets 500mg
linagliptin placeboDrug
linagliptin placebo tablets 5mg
metforminDrug
metformin tablets 500mg
metforminDrug
metformin tablets 500 mg
linagliptinDrug
linagliptin tablets 5mg

Study groups in NCT01438814
Study group	Role	What they receive
linagliptin + metformin	Experimental	patients to receive linagliptin +metformin QD Receives: Drug: metformin; Drug: linagliptin
metformin	Active comparator	patients to receive metformin BID Receives: Drug: metformin placebo; Drug: linagliptin placebo; Drug: metformin

What is being measured

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

Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment
Adjusted mean change in HbA1c from baseline at Week 14 was analysed using an ANCOVA model. The Model included treatment and continuous baseline HbA1c.
Measured: Baseline and 14 weeks

Secondary outcomes (12)

Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 14 Weeks of Treatment, on no Occurrence of Moderate or Severe Gastrointestinal (GI) Side Effects During 14 Weeks of Treatment
The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 7.0% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe gastrointestinal (GI) side effects of metformin, as assessed by the investigators during 14 weeks of treatment)
Measured: 14 weeks
Occurence of Metformin Pre-specified Moderate to Severe GI Side Effects Assessed by Investigators During 14 Weeks of Treatment
Proportion of patients who experienced at least one metformin pre-specified moderate or severe GI side effect during 14 weeks
Measured: 14 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 14 Weeks of Treatment
Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.
Measured: Baseline and 14 weeks
Metformin Pre-specified GI Symptom Intensity Score Assessed by Investigators During 14 Weeks of Treatment
Patients could experience multiple events, therefore, multiple answers were possible for each patient.
Measured: 14 weeks
Metformin Pre-specified GI Symptom Intensity Score Assessed by Patients During 14 Weeks of Treatment
The intensity of the GI side effects was also assessed by the patients using VAS scaled from 0 to 10; higher scores indicate more severe events. Means are adjusted by treatment and continuous baseline HbA1c.
Measured: 14 weeks
Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 14 Weeks of Treatment, and no Occurrence of Moderate or Severe Metformin Pre-specified GI Side Effects Assessed by Investigators
The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 6.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).
Measured: 14 weeks
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment)
The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.5% after 14 weeks of treatment).
Measured: 14 weeks
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment)
The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.8% after 14 weeks of treatment).
Measured: 14 weeks
Composite Endpoint of Occurence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment) and no Occurence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by the Investigators During 14 Weeks
The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).
Measured: 14 weeks
Change From Baseline in Body Weight by Visit at Week 14
Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline weight
Measured: Baseline and 14 weeks
Composite Endpoint of Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment) and no Occurrence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by Investigators During 14 Weeks
The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.8% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).
Measured: 14 weeks
Change From Baseline in HbA1c Over Time
Means are adjusted by treatment and continuous baseline HbA1c
Measured: Baseline, 2 weeks and 8 weeks

Timeline

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

Nov 2011Mar 2013

First posted22 Sep 2011 (estimated)
Study startNov 2011
Primary completionMar 2013
Study completionMar 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 (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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 689 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01438814
Sponsor's protocol ID: 1218.60
Other IDs: 2011-002276-16
Status last verified: Nov 2014
First submitted: 21 Sep 2011
Last updated: 25 Nov 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Ji L, Zinman B, Patel S, Ji J, Bailes Z, Thiemann S, Seck T. Efficacy and safety of linagliptin co-administered with low-dose metformin once daily versus high-dose metformin twice daily in treatment-naive patients with type 2 diabetes: a double-blind randomized trial. Adv Ther. 2015 Mar;32(3):201-15. doi: 10.1007/s12325-015-0195-3. Epub 2015 Mar 25.
PubMed 25805187

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 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Double-dummy, Active-comparator Controlled Study Investigating the Efficacy and Safety of Linagliptin Co-administered With Metformin QD at Evening Time Versus Metformin BID Over 14 Weeks in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control
ClinicalTrials.gov ID: NCT01438814
Acronym / sponsor ID: 1218.60
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 689 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Nov 2011
Primary completion: Mar 2013 (actual)
Study completion: Mar 2013 (actual)
First posted: 22 Sep 2011 (estimated)
Results: Posted 3 Jun 2014

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: 2

Arm	Type	Receives
linagliptin + metformin	Experimental	Drug: metformin, Drug: linagliptinpatients to receive linagliptin +metformin QD
metformin	Active comparator	Drug: metformin placebo, Drug: linagliptin placebo, Drug: metforminpatients to receive metformin BID

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 naive, defined as absence of any oral antidiabetic therapy or insulin for 12 weeks prior to randomization
Glycosylated haemoglobin A1c (HbA1c) >/= 7.0% (53 mmol/mol) to </= 10.0% (86 mmol/mol) at visit 1 (screening);
Age>/=18 and </=80 years at visit 1(screening);
Body Mass Index (BMI)</= 45kg/m2 at visit 1 (screening);

Key exclusion criteria (18 listed)

Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (13.3mmol/L) after an overnight fast during screening/placebo run-in and confirmed by a second measurement (Not on the same day);
Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization
Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or Transient ischemia attack (TIA) within 3 months prior to informed consent;
Indication of liver disease/Impaired hepatic function, defined by serum levels of either Aspartate aminotransferase (ALT or SGPT), alanine aminotransferase (AST or SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at visit 1 and/or run-in phase,
Impaired renal function, defined as eGFR< 60ml/min (moderate or severe renal impairment, modification of diet in renal disease (MDRD) formula) as determined during screening or at run-in phase

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
metformin placebometformin placebo tablets 500mg	Drug	metformin
linagliptin placebolinagliptin placebo tablets 5mg	Drug	metformin
metforminmetformin tablets 500mg	Drug	metformin
metforminmetformin tablets 500 mg	Drug	linagliptin + metformin
linagliptinlinagliptin tablets 5mg	Drug	linagliptin + metformin

Primary outcome

Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment
Time frame: Baseline and 14 weeks
Adjusted mean change in HbA1c from baseline at Week 14 was analysed using an ANCOVA model. The Model included treatment and continuous baseline HbA1c.

12 secondary outcomes

Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 14 Weeks of Treatment, on no Occurrence of Moderate or Severe Gastrointestinal (GI) Side Effects During 14 Weeks of Treatment
Time frame: 14 weeks
Occurence of Metformin Pre-specified Moderate to Severe GI Side Effects Assessed by Investigators During 14 Weeks of Treatment
Time frame: 14 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 14 Weeks of Treatment
Time frame: Baseline and 14 weeks
Metformin Pre-specified GI Symptom Intensity Score Assessed by Investigators During 14 Weeks of Treatment
Time frame: 14 weeks
Metformin Pre-specified GI Symptom Intensity Score Assessed by Patients During 14 Weeks of Treatment
Time frame: 14 weeks
Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 14 Weeks of Treatment, and no Occurrence of Moderate or Severe Metformin Pre-specified GI Side Effects Assessed by Investigators
Time frame: 14 weeks
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment)
Time frame: 14 weeks
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment)
Time frame: 14 weeks
Composite Endpoint of Occurence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment) and no Occurence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by the Investigators During 14 Weeks
Time frame: 14 weeks
Change From Baseline in Body Weight by Visit at Week 14
Time frame: Baseline and 14 weeks
Composite Endpoint of Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment) and no Occurrence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by Investigators During 14 Weeks
Time frame: 14 weeks
Change From Baseline in HbA1c Over Time
Time frame: Baseline, 2 weeks and 8 weeks

Results and safety

Results posted to the registry on 3 Jun 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lina 5mg + Met qd	344	330
Met Bid	345	331

Primary outcome: Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment

Time frame: Baseline and 14 weeks. Mean (Standard Error). Unit: percent

Measure	Lina 5mg + Met qd n = 298	Met Bid n = 341
Value	-0.99 (0.05)	-0.98 (0.04)

Lina 5mg + Met qd vs Met Bid: Mean Difference (Final Values): -0.01 (95% CI -0.13 to 0.12), p <0.0001, ANCOVA
Lina 5mg + Met qd vs Met Bid: Mean Difference (Final Values): -0.01 (95% CI -0.13 to 0.12), p = 0.8924, ANCOVA

Population analysed: FAS1000mg with last observation carried forward (LOCF): all patients randomised and treated who had a baseline at least 1 on-treatment HbA1c value and who tolerated a daily metformin dose of at least 1000 mg at the end of the titration phase.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 14 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lina 5mg + Met qd	2 of 344 (0.6%)	101 of 344 (29.4%)	Not reported
Met Bid	7 of 345 (2%)	121 of 345 (35.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25805187Ji L, Zinman B, Patel S, Ji J, Bailes Z, Thiemann S, Seck T. Efficacy and safety of linagliptin co-administered with low-dose metformin once daily versus high-dose metformin twice daily in treatment-naive patients with type 2 diabetes: a double-blind randomized trial. Adv Ther. 2015 Mar;32(3):201-15. doi: 10.1007/s12325-015-0195-3. Epub 2015 Mar 25.
Related InfoLink provided by the sponsor.

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Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

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

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing metformin and linagliptin in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 90 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 6 inclusion and 18 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 25 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 90 sites in Canada, China, Spain, Germany, India 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 3 Jun 2014). 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 From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment (time frame: Baseline and 14 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 NCT01438814, 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 25 Nov 2014.