DiabetesPhase 3NCT00620282

The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus

A Phase 3 study testing liraglutide and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 1 site in United States.

Completed

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

Official record

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Trial summary

This trial is conducted in the United States of America (USA). The purpose of the trial is to assess the effect of liraglutide on forearm blood flow in subjects with type 2 diabetes who are on diet and lifestyle changes or treated with metformin alone. Read more about this study

Who is it for?: Ages 40 to 70 years
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: liraglutide and glimepiride
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 1 siteUnited States
Study dates: Feb 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 40 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Type 2 diabetes
Diet and lifestyle changes or metformin monotherapy for at least three months
HbA1c (glycosylated haemoglobin) 6.5-9.0% (both inclusive)
Body Mass Index (BMI) less than or equal to 40 kg/m^2

Who cannot join

Previous treatment with insulin (except for short term treatment with insulin in connection with intercurrent illness, at the discretion of the Investigator)
Previous treatment with glucagon-like peptide-1 (GLP-1) analogues/mimetics, including treatment in a clinical trial
Treatment with any oral hypoglycaemic agents other than metformin in a period of 3 months prior to screening
Current smoker or history of smoking within 6 months prior to screening
Evidence of overt cardiovascular disease (documented coronary heart disease, class II-IV congestive heart failure, cerebrovascular disease, or peripheral vascular disease)
Abnormal, clinically significant exercise stress electrocardiogram (ECG) test, as judged by the Investigator

Show all 10Show fewer

Known retinopathy or maculopathy requiring acute treatment, as judged by the Investigator
Known autonomic neuropathy, as judged by the Investigator
Initiation or change (dose or treatment regimen) in concomitant blood pressure-lowering or lipid-lowering medication within 4 weeks prior to screening
Systolic blood pressure more than or equal to 140 mmHg and/or diastolic blood pressure more than or equal to 90 mmHg

Trial locations and contacts

1 site in 1 country.

United States1 site

Novo Nordisk Investigational Site
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride Arm

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, placebo, glimepiride
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
Stepwise dose increase, s.c. (under the skin) injection, once daily
placeboDrug
Liraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily
glimepirideDrug
Tablets, 1 - 4 mg daily

Study groups in NCT00620282
Study group	Role	What they receive
Lira 1.8	Experimental	Liraglutide 1.8 mg administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) Receives: Drug: liraglutide
Placebo	Placebo comparator	Placebo administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) Receives: Drug: placebo
Glimepiride	Active comparator	Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 Receives: Drug: glimepiride

What is being measured

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

Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)
Assessed endothelial function by measuring the change in ACh-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.
Measured: week 0, week 12

Secondary outcomes (13)

Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF)
Assessed endothelial function by measuring the change in SNP-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.
Measured: week 0, week 12
Change in HbA1c (Glycosylated Haemoglobin A1c)
Percentage point change in HbA1c
Measured: week 0, week 12
Change in Fasting Plasma Glucose (FPG)
Change in FPG
Measured: week 0, week 12
Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles
The 7-point profile included plasma glucose measurements at the following time points: before each main meal (breakfast, lunch and dinner), 90 minutes after the start of each main meal (breakfast, lunch and dinner) and at bedtime.
Measured: week 0, week 12
Change in Body Weight
Measured: week 0, week 12
Fasting Lipid Profile - Change in Total Cholesterol (TC)
Change in TC
Measured: week 0, week 12
Fasting Lipid Profile - Change in LDL-C
Change in LDL-C
Measured: week 0, week 12
Fasting Lipid Profile - Change in HDL-C
Change in HDL-C
Measured: week 0, week 12
Fasting Lipid Profile - Change in Triglycerides (TG)
Change in TG
Measured: week 0, week 12
Biomarkers of Cardiovascular Risk - Change in TNF-alpha
Change in TNF-alpha
Measured: week 0, week 12
Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range
Number of subjects with serum BUN values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 6.000 mg/dL, upper value 21.000 mg/dL) Male (lower value 8.000 mg/dL, upper value 25.000 mg/dL).
Measured: week 0, week 12
Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range
Number of subjects with serum creatinine values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 0.600 mg/dL, upper value 1.100 mg/dL) Male (lower value 0.800 mg/dL, upper value 1.300 mg/dL).
Measured: week 0, week 12
Number of Hypoglycaemic Episodes
Total number of hypoglycaemic episodes occurring from week 0 to week 12. Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself and either plasma glucose was below 56 mg/dL or symptoms were reversed after food intake or glucagon/intravenous glucose administration. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.
Measured: weeks 0-12

Timeline

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

Feb 2008May 2010

First posted21 Feb 2008 (estimated)
Study startFeb 2008
Primary completionMay 2010
Study 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 (3)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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00620282
Sponsor's protocol ID: NN2211-1799
Status last verified: Jan 2017
First submitted: 11 Feb 2008
Last updated: 8 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
PubMed 23010561
Nandy D, Johnson C, Basu R, Joyner M, Brett J, Svendsen CB, Basu A. The effect of liraglutide on endothelial function in patients with type 2 diabetes. Diab Vasc Dis Res. 2014 Nov;11(6):419-30. doi: 10.1177/1479164114547358. Epub 2014 Sep 11.
PubMed 25212693
Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12.
PubMed 25504028

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 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride Arm
ClinicalTrials.gov ID: NCT00620282
Acronym / sponsor ID: NN2211-1799
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: May 2010 (actual)
Study completion: May 2010 (actual)
First posted: 21 Feb 2008 (estimated)
Results: Posted 15 Jun 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 (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Lira 1.8	Experimental	Drug: liraglutideLiraglutide 1.8 mg administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)
Placebo	Placebo comparator	Drug: placeboPlacebo administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)
Glimepiride	Active comparator	Drug: glimepirideGlimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12

Who may qualify

Ages: 40 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Type 2 diabetes
Diet and lifestyle changes or metformin monotherapy for at least three months
HbA1c (glycosylated haemoglobin) 6.5-9.0% (both inclusive)
Body Mass Index (BMI) less than or equal to 40 kg/m^2

Key exclusion criteria (10 listed)

Previous treatment with insulin (except for short term treatment with insulin in connection with intercurrent illness, at the discretion of the Investigator)
Previous treatment with glucagon-like peptide-1 (GLP-1) analogues/mimetics, including treatment in a clinical trial
Treatment with any oral hypoglycaemic agents other than metformin in a period of 3 months prior to screening
Current smoker or history of smoking within 6 months prior to screening
Evidence of overt cardiovascular disease (documented coronary heart disease, class II-IV congestive heart failure, cerebrovascular disease, or peripheral vascular disease)

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
liraglutideStepwise dose increase, s.c. (under the skin) injection, once daily	Drug	Lira 1.8
placeboLiraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily	Drug	Placebo
glimepirideTablets, 1 - 4 mg daily	Drug	Glimepiride

Primary outcome

Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)
Time frame: week 0, week 12
Assessed endothelial function by measuring the change in ACh-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.

13 secondary outcomes

Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF)
Time frame: week 0, week 12
Change in HbA1c (Glycosylated Haemoglobin A1c)
Time frame: week 0, week 12
Change in Fasting Plasma Glucose (FPG)
Time frame: week 0, week 12
Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles
Time frame: week 0, week 12
Change in Body Weight
Time frame: week 0, week 12
Fasting Lipid Profile - Change in Total Cholesterol (TC)
Time frame: week 0, week 12
Fasting Lipid Profile - Change in LDL-C
Time frame: week 0, week 12
Fasting Lipid Profile - Change in HDL-C
Time frame: week 0, week 12
Fasting Lipid Profile - Change in Triglycerides (TG)
Time frame: week 0, week 12
Biomarkers of Cardiovascular Risk - Change in TNF-alpha
Time frame: week 0, week 12
Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range
Time frame: week 0, week 12
Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range
Time frame: week 0, week 12
Number of Hypoglycaemic Episodes
Time frame: weeks 0-12

Results and safety

Results posted to the registry on 15 Jun 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
Lira 1.8	16	16
Placebo	16	14
Glimepiride	17	16

Primary outcome: Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)

Time frame: week 0, week 12. Least squares mean (Standard Error). Unit: mL/100 mL/min

Measure	Lira 1.8 n = 16	Placebo n = 14	Glimepiride n = 16
Value	4.244 (2.551)	-3.187 (2.758)	2.164 (2.568)

Lira 1.8 vs Placebo: Least squares mean: 7.43 (95% CI -0.164 to 15.025), p = 0.0549, ANCOVA
Lira 1.8 vs Glimepiride: Least squares mean: 2.08 (95% CI -5.215 to 9.375), p = 0.5681, ANCOVA
Placebo vs Glimepiride: Least squares mean: 5.35 (95% CI -2.323 to 13.024), p = 0.1668, ANCOVA

Population analysed: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse events were collected from week 0 to week 12.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lira 1.8	0 of 16 (0%)	11 of 16 (68.8%)	Not reported
Placebo	1 of 16 (6.3%)	9 of 16 (56.3%)	Not reported
Glimepiride	0 of 17 (0%)	5 of 17 (29.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23010561Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
Results publication: PubMed 25212693Nandy D, Johnson C, Basu R, Joyner M, Brett J, Svendsen CB, Basu A. The effect of liraglutide on endothelial function in patients with type 2 diabetes. Diab Vasc Dis Res. 2014 Nov;11(6):419-30. doi: 10.1177/1479164114547358. Epub 2014 Sep 11.
Results publication: PubMed 25504028Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12.
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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing liraglutide and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 1 site in United States.

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 10 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 8 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 15 Jun 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?

Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) (time frame: week 0, week 12). 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 NCT00620282, which also lists 3 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 8 Mar 2017.