Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LIRAFLAME)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03449654 |
Recruitment Status :
Completed
First Posted : February 28, 2018
Last Update Posted : June 11, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
The objective of this study is to evaluate the mechanism behind the anti-atherogenic effects of liraglutide.
In a randomized, placebo-controlled, double-blind, parallel trial we will included 100 patients with type 2 diabetes. Patients will be randomized 1:1 to an active treatment period of 26 weeks or placebo for 26 weeks.
The primary endpoint is change from baseline to week 26 in vascular inflammation, assessed by Flour Deoxy Glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT)
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Diabetes Mellitus, Type 2 | Drug: Liraglutide Drug: Placebo (for liraglutide) | Phase 4 |
Despite multifactorial treatment patients with type 2 diabetes are still at high risk of cardiovascular disease. The clinical LEADER trial demonstrated a reduction in cardiovascular events in patients with type 2 diabetes treated with the GLP-1 receptor agonist liraglutide and there are a number of studies indicating that liraglutide has a positive effect on the vascular phenotype. Several of the animal or ex vivo studies suggest an anti-inflammatory mechanism behind this effect. However, no in vivo human studies have been undertaken to test this hypothesis and it would be of significance to determine the precise mechanism since atherosclerosis has large prognostic impact in patients with type 2 diabetes.
The objective of this study is to evaluate the mechanism behind the anti-atherogenic effects of liraglutide.
In a randomized, placebo-controlled, double-blind, parallel trial we will included 100 patients with type 2 diabetes. Patients will be randomized 1:1 to an active treatment period of 26 weeks or placebo for 26 weeks.
The primary endpoint is change from baseline to week 26 in vascular inflammation, assessed by Flour Deoxy Glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT). FDG-PET/CT is currently the only clinically available technique for specific in vivo evaluation of vascular inflammation and for quantification of the effects of medical intervention on plaque inflammation. FDG-PET of arteries has been proven very reproducible and therefore has high power to show a treatment effect in a smaller group of patients.
A number of complementary methods exist that assess different steps in the atherogenesis like endothelial function (e.g. endo-PAT, glycocalyx measurement), artery wall thickening (e.g. carotid intima media thickness), or coronary atherosclerosis (e.g. coronary artery calcium score). For comparison these other methods will be included as secondary endpoints as they are generally more accessible and less expensive.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 102 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Randomized, Placebo-controlled, Parallel |
Masking: | Double (Participant, Investigator) |
Masking Description: | Dobbelt-blinded |
Primary Purpose: | Prevention |
Official Title: | Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes: A Randomized, Placebo-controlled, Double-blind, Parallel Clinical PET/CT Trial The Liraflame Trial |
Actual Study Start Date : | October 26, 2017 |
Actual Primary Completion Date : | August 16, 2019 |
Actual Study Completion Date : | August 16, 2019 |

Arm | Intervention/treatment |
---|---|
Liraglutide |
Drug: Liraglutide
Liraglutid |
placebo |
Drug: Placebo (for liraglutide)
Placebo (for liraglutide) |
- Change in vascular inflammation [ Time Frame: baseline to week 26 ]Change in vascular inflammation assessed by FDG PET/CT
- Change in Endothelial dysfunction [ Time Frame: baseline to week 26 ]Change in endothelial dysfunction assessed with endo-PAT
- Change in Endothelial dysfunction [ Time Frame: baseline to week 13 and 26 ]Change in endothelial dysfunction, assessed as sublingual glycocalyx measurement
- Coronary artery calcium score [ Time Frame: baseline to week 26 ]Change coronary artery calcium score (absolute values)
- Carotid intima media thickness [ Time Frame: baseline to week 26 ]Change in carotid intima media thickness measured by ultrasound
- Autonomic nervous system function [ Time Frame: baseline to week 26 ]Change in cardiovascular autonomic neuropathy indices

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Given written informed consent
- Male or female patients >50 years with type 2 diabetes (WHO criteria)
- HbA1c ≥ 48 mmol/mol (6.5 %)
- eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-epi formula)
- Stable glucose-lowering medication (excluding oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and other agents, which in the investigator's opinion could interfere with the effect of liraglutide)for at least 4 weeks before the baseline PET/CT
- Stable/no treatment of hypercholesterolemia 4 weeks before baseline PET/CT
- Must be able to communicate with the investigator and understand informed consent.
Exclusion Criteria:
- Type 1 diabetes mellitus
- Chronic pancreatitis / previous acute pancreatitis
- Known or suspected hypersensitivity to trial product(s) or related products
- Treatment 90 days prior to screening with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and other agents, which in the investigator's opinion could interfere with the effect of liraglutide
- Cancer or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
- Clinical signs of diabetic gastroparesis
- Previous bowel resection
- Impaired liver function (transaminases > two times upper reference levels)
- Inflammatory bowel disease
- Weight >150 kg
- Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
- Known or suspected abuse of alcohol or narcotics
- Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449654
Denmark | |
Steno Diabetes Center Copenhagen | |
Gentofte, Denmark, 2820 |
Responsible Party: | Peter Rossing, MD, chief phycisian, Dr. Med., Steno Diabetes Center Copenhagen |
ClinicalTrials.gov Identifier: | NCT03449654 |
Other Study ID Numbers: |
H-16044546 |
First Posted: | February 28, 2018 Key Record Dates |
Last Update Posted: | June 11, 2020 |
Last Verified: | June 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Diabetes Mellitus Diabetes Mellitus, Type 2 Inflammation Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Pathologic Processes |
Liraglutide Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |