DiabetesPhase 4LIRA-LIXI™NCT01973231

Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes

A Phase 4 study testing liraglutide and lixisenatide in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 61 sites in 9 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

This trial is conducted in Europe. The aim of the trial is to investigate the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in subjects with type 2 diabetes (T2DM). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: liraglutide and lixisenatide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 404 participants
Where: 61 sitesin 9 countries
Study dates: Oct 2013to Nov 2014
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
Subjects diagnosed with T2DM and on unchanged metformin treatment at the maximum tolerated dose (at least 1000 mg/day and up to 3000 mg/day) for at least 90 days prior to screening
HbA1c 7.5 - 10.5% (53 mmol/mol - 91 mmol/mol) (both inclusive)
Body Mass Index (BMI) equal to or above 20 kg/m^2

Who cannot join

Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods. (Adequate contraceptive measures as required by local law or practice)
Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with intercurrent illness
History of chronic pancreatitis or idiopathic acute pancreatitis
Screening calcitonin value equal to or above 50 ng/L
Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)
Impaired liver function, defined as alanine aminotransferase (ALAT) equal to or above 2.5 times upper normal limit (UNL)

Show all 11Show fewer

Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula
Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event as judged by the investigator within 90 days prior to screening
Heart failure, New York Heart Association (NYHA) class IV
Uncontrolled hypertension (defined as systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg)
Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

Trial locations and contacts

61 sites in 9 countries.

Country

City, postcode or hospital

61 sites in 9 countries

United Kingdom12 sites

Novo Nordisk Investigational Site
Basingstoke, RG24 9GT
Novo Nordisk Investigational Site
Bristol, BS10 5NB
Novo Nordisk Investigational Site
Chester, CH2 1UL
Novo Nordisk Investigational Site
Chiswick, W4 3JL
Novo Nordisk Investigational Site
Coventry, CV2 2DX
Novo Nordisk Investigational Site
Derby, DE22 3NE
Novo Nordisk Investigational Site
Devon, EX2 5DW
Novo Nordisk Investigational Site
Great Yarmouth, NR31 6LA
Novo Nordisk Investigational Site
Lancaster, LA1 1RP
Novo Nordisk Investigational Site
Plymouth, PL6 8BQ
Novo Nordisk Investigational Site
Sandbach, CW11 1EQ
Novo Nordisk Investigational Site
Taunton, TA1 5DA

Other trials in United Kingdom

Germany9 sites

Novo Nordisk Investigational Site
Bad Lauterberg im Harz, 37431
Novo Nordisk Investigational Site
Berlin, 13055
Novo Nordisk Investigational Site
Bochum, 44869
Novo Nordisk Investigational Site
Dresden, 01219
Novo Nordisk Investigational Site
Duisburg, 47051
Novo Nordisk Investigational Site
Friedrichsthal, 66299
Novo Nordisk Investigational Site
Lampertheim, 68623
Novo Nordisk Investigational Site
Ludwigshafen, 67059
Novo Nordisk Investigational Site
Saint Ingbert, 66386

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Hungary8 sites

Novo Nordisk Investigational Site
Baja, 6500
Novo Nordisk Investigational Site
Budapest, 1042
Novo Nordisk Investigational Site
Budapest, 1089
Novo Nordisk Investigational Site
Budapest, 1125
Novo Nordisk Investigational Site
Gyula, 5700
Novo Nordisk Investigational Site
Pécs, 7623
Novo Nordisk Investigational Site
Salgótarján, 3100
Novo Nordisk Investigational Site
Szeged, H-6720

Other trials in Hungary

France7 sites

Novo Nordisk Investigational Site
Boulogne-Billancourt, 92100
Novo Nordisk Investigational Site
Corbeil-Essonnes, 91106
Novo Nordisk Investigational Site
Hinx, 40180
Novo Nordisk Investigational Site
La Rochelle, 17019
Novo Nordisk Investigational Site
Saint-Herblain, 44800
Novo Nordisk Investigational Site
Strasbourg, 67000
Novo Nordisk Investigational Site
Vénissieux, 69200

Other trials in France

Czechia5 sites

Novo Nordisk Investigational Site
Hradec Králové, 50005
Novo Nordisk Investigational Site
Mladá Boleslav, 293 50
Novo Nordisk Investigational Site
Olomouc, 77900
Novo Nordisk Investigational Site
Pilsen, 32600
Novo Nordisk Investigational Site
Prostějov, 79601

Other trials in Czechia

Finland5 sites

Novo Nordisk Investigational Site
Helsinki, 00260
Novo Nordisk Investigational Site
Jyväskylä, 40100
Novo Nordisk Investigational Site
Oulu, FI-90220
Novo Nordisk Investigational Site
Pori, FI-28120
Novo Nordisk Investigational Site
Rovaniemi, 96400

Other trials in Finland

Italy5 sites

Novo Nordisk Investigational Site
Catania, 95122
Novo Nordisk Investigational Site
Cittadella (PD), 35013
Novo Nordisk Investigational Site
Padova, 35143
Novo Nordisk Investigational Site
Palermo, 90129
Novo Nordisk Investigational Site
Terni, 05100

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Latvia5 sites

Novo Nordisk Investigational Site
Ogre, LV-5001
Novo Nordisk Investigational Site
Riga, LV-1002
Novo Nordisk Investigational Site
Riga, LV-1012
Novo Nordisk Investigational Site
Riga, LV-1024
Novo Nordisk Investigational Site
Riga, LV-1038

Other trials in Latvia

Lithuania5 sites

Novo Nordisk Investigational Site
Kaunas, 48259
Novo Nordisk Investigational Site
Kaunas, 50009
Novo Nordisk Investigational Site
Klaipėda, 94198
Novo Nordisk Investigational Site
Šiauliai, 76231
Novo Nordisk Investigational Site
Vilnius, 08661

Other trials in Lithuania

About this study

This trial is conducted in Europe. The aim of the trial is to investigate the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in subjects with type 2 diabetes (T2DM).

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, lixisenatide
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

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

liraglutideDrug
Starting dose of 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day is reached. Administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial metformin (equal to or above 1000 mg/day and up to 3000 mg/day).
lixisenatideDrug
Starting dose of 10 microg to be administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (equal to or above 1000mg/day and up to 3000mg/day). Dose escalation to 20 microg s.c. once daily from day 15 after randomization.

Study groups in NCT01973231
Study group	Role	What they receive
Metformin + liraglutide 1.8 mg	Experimental	Not described Receives: Drug: liraglutide
Metformin + lixisenatide 20 microg	Active comparator	Not described Receives: Drug: lixisenatide

What is being measured

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

Change in Glycosylated Haemoglobin (HbA1c) From Baseline
Change from baseline in HbA1c after 26 weeks of treatment.
Measured: Week 0, week 26

Secondary outcomes (6)

Change in Fasting Plasma Glucose (FPG) From Baseline
Change from baseline in FPG after 26 weeks of treatment.
Measured: Week 0, week 26
Change in Body Weight From Baseline
Change from baseline in body weight after 26 weeks of treatment.
Measured: Week 0, week 26
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)
Subjects who achieved HbA1c below 7.0% (53 mmol/mol) after 26 weeks of treatment (yes/no).
Measured: After 26 weeks of treatment
Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no)
Subjects who achieved HbA1c below equal to or below 6.5% (48 mmol/mol) after 26 weeks of treatment (yes/no).
Measured: After 26 weeks of treatment
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no)
Subjects who achieved HbA1c below 7.0% (53 mmol/mol) and no weight gain after 26 weeks of treatment (yes/no).
Measured: After 26 weeks of treatment
Number of Treatment Emergent Adverse Events (TEAEs)
A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator.
Measured: Weeks 0-26

Timeline

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

Oct 2013Nov 2014

First posted31 Oct 2013 (estimated)
Study startOct 2013
Primary completionNov 2014
Study completionNov 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 (2)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe 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: None (open label)
Enrolment: 404 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01973231
Sponsor's protocol ID: NN2211-3867
Other IDs: 2012-004984-27, U1111-1136-3644
Acronym: LIRA-LIXI™
Status last verified: Dec 2016
First submitted: 23 Oct 2013
Last updated: 9 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Nauck M, Rizzo M, Johnson A, Bosch-Traberg H, Madsen J, Cariou B. Once-Daily Liraglutide Versus Lixisenatide as Add-on to Metformin in Type 2 Diabetes: A 26-Week Randomized Controlled Clinical Trial. Diabetes Care. 2016 Sep;39(9):1501-9. doi: 10.2337/dc15-2479. Epub 2016 Jun 16.
PubMed 27311491
Hunt B, Vega-Hernandez G, Valentine WJ, Kragh N. Evaluation of the long-term cost-effectiveness of liraglutide vs lixisenatide for treatment of type 2 diabetes mellitus in the UK setting. Diabetes Obes Metab. 2017 Jun;19(6):842-849. doi: 10.1111/dom.12890. Epub 2017 Feb 23.
PubMed 28124820

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 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes
ClinicalTrials.gov ID: NCT01973231
Acronym / sponsor ID: LIRA-LIXI™ / NN2211-3867
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 404 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Oct 2013
Primary completion: Nov 2014 (actual)
Study completion: Nov 2014 (actual)
First posted: 31 Oct 2013 (estimated)
Results: Posted 22 Dec 2015

Clinical summary

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

This trial is conducted in Europe. The aim of the trial is to investigate the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in subjects with type 2 diabetes (T2DM).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Metformin + liraglutide 1.8 mg	Experimental	Drug: liraglutide
Metformin + lixisenatide 20 microg	Active comparator	Drug: lixisenatide

Who may qualify

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

Key inclusion criteria (4 listed)

Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
Subjects diagnosed with T2DM and on unchanged metformin treatment at the maximum tolerated dose (at least 1000 mg/day and up to 3000 mg/day) for at least 90 days prior to screening
HbA1c 7.5 - 10.5% (53 mmol/mol - 91 mmol/mol) (both inclusive)
Body Mass Index (BMI) equal to or above 20 kg/m^2

Key exclusion criteria (11 listed)

Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods. (Adequate contraceptive measures as required by local law or practice)
Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with intercurrent illness
History of chronic pancreatitis or idiopathic acute pancreatitis
Screening calcitonin value equal to or above 50 ng/L
Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)

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
liraglutideStarting dose of 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day is reached. Administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial metformin (equal to or above 1000 mg/day and up to 3000 mg/day).	Drug	Metformin + liraglutide 1.8 mg
lixisenatideStarting dose of 10 microg to be administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (equal to or above 1000mg/day and up to 3000mg/day). Dose escalation to 20 microg s.c. once daily from day 15 after randomization.	Drug	Metformin + lixisenatide 20 microg

Primary outcome

Change in Glycosylated Haemoglobin (HbA1c) From Baseline
Time frame: Week 0, week 26
Change from baseline in HbA1c after 26 weeks of treatment.

6 secondary outcomes

Change in Fasting Plasma Glucose (FPG) From Baseline
Time frame: Week 0, week 26
Change in Body Weight From Baseline
Time frame: Week 0, week 26
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)
Time frame: After 26 weeks of treatment
Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no)
Time frame: After 26 weeks of treatment
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no)
Time frame: After 26 weeks of treatment
Number of Treatment Emergent Adverse Events (TEAEs)
Time frame: Weeks 0-26

Results and safety

Results posted to the registry on 22 Dec 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
Liraglutide	202	191
Lixisenatide	202	190

Primary outcome: Change in Glycosylated Haemoglobin (HbA1c) From Baseline

Time frame: Week 0, week 26. Mean (Standard Deviation). Unit: Percent (%) glycosylated haemoglobin

Measure	Liraglutide n = 194	Lixisenatide n = 191
Value	-1.809 (0.9159)	-1.238 (1.0085)

Population analysed: The full analysis set (FAS) included all randomised subjects. Missing values were imputed using predicted values from the mixed model for repeated measurements (MMRM) model. Due to missing HbA1c post baseline data, 194 and 191 subjects in liraglutide and lixisenatide treatment group, respectively were included in the HbA1c analysis.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Weeks 0-26. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Liraglutide	12 of 202 (5.9%)	90 of 202 (44.6%)	Not reported
Lixisenatide	7 of 202 (3.5%)	83 of 202 (41.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27311491Nauck M, Rizzo M, Johnson A, Bosch-Traberg H, Madsen J, Cariou B. Once-Daily Liraglutide Versus Lixisenatide as Add-on to Metformin in Type 2 Diabetes: A 26-Week Randomized Controlled Clinical Trial. Diabetes Care. 2016 Sep;39(9):1501-9. doi: 10.2337/dc15-2479. Epub 2016 Jun 16.
Derived from this study: PubMed 28124820Hunt B, Vega-Hernandez G, Valentine WJ, Kragh N. Evaluation of the long-term cost-effectiveness of liraglutide vs lixisenatide for treatment of type 2 diabetes mellitus in the UK setting. Diabetes Obes Metab. 2017 Jun;19(6):842-849. doi: 10.1111/dom.12890. Epub 2017 Feb 23.
Clinical Trials at Novo NordiskLink 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.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

61 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing liraglutide and lixisenatide in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 61 sites in 9 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 4 inclusion and 11 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 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in United Kingdom, Germany, Hungary, France, Czechia and 4 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 22 Dec 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?

Change in Glycosylated Haemoglobin (HbA1c) From Baseline (time frame: Week 0, week 26). 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 NCT01973231, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2017.