Liraglutide Effects on Epicardial Fat Inflammatory Genes

NCT ID: NCT03260881

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2024-09-05

Brief Summary

Epicardial adipose tissue (EAT) is the visceral fat of the heart. EAT could locally affect the coronary arteries through local secretion of pro-inflammatory cytokines. EAT plays a role in the development of the coronary artery disease (CAD). EAT is a highly enriched with genes involved in inflammation. Given its rapid metabolism and simple measurability, as first developed by Iacobellis, EAT serves as target for medications targeting the fat. Glucagon-like peptide-1 agonists (GLP-1A) are anti-diabetic medications with recently suggested cardio-protective properties. Liraglutide, a GLP-1A, has recently shown to reduce the cardiovascular risk. Iacobellis'group found that EAT thickness decreased by an unprecedented 36% after 12 weeks of treatment with liraglutide. Remarkably, Iacobellis'group found for the first time that human EAT express GLP-1 Receptor (GLP-1R). GLP-1A effects may be therefore visceral fat specific and target EAT. Based on these preliminary data, we hypothesize that treatment with liraglutide will significantly and rapidly reduce EAT inflammation. Decreased EAT inflammation can reduce the burden of the coronary plaques. We will test our hypothesis in a 12-week randomized, double-blind, placebo-controlled, interventional study in 40 patients with type 2 diabetes mellitus (T2DM), and CAD, with an acceptable glycemic control on their current diabetes regimen who require elective coronary artery bypass graft (CABG) regardless of their participation in the study. A minimum time frame of 3-week treatment will be considered to detect significant changes in the study endpoints. Inclusion criteria for body fat markers will rule out the confounding effect of different body fast distribution at baseline. Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide or to remain on current treatment/ placebo prior to cardiac surgery. CAD subjects not allocated to liraglutide will be started on a supervised low-calorie diet (LCD) to achieve approximately 5% of weight loss after from a minimum of 3 weeks up to 12 weeks to avoid the confounding effect of weight loss on the study outcomes. Fat samples will be collected during cardiac surgery after up to 12 weeks of treatment either with liraglutide or placebo and processed for analysis of mRNA and protein expression of EAT and SAT inflammatory genes such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin 6 (IL-6), and GLP-1R.

Conditions

Type2 Diabetes; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

L-group

• L-group will be started on liraglutide. Liraglutide will be started and administered for from a minimum of 4 weeks up to 12 weeks prior to CABG with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). The dose of 1.8 mg daily will be maintained until the end of the 12-week study. Other and current diabetes treatment will be continued

Group Type: ACTIVE_COMPARATOR

Liraglutide Pen Injector [Victoza]

Intervention Type: DRUG

Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).

D-group

placebo will be administered in addition to current treatment prior to the CABG with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). D-group will be started on a supervised low calorie diet (LCD) to achieve approximately 5% of weight loss after from a minimum of 4 weeks up to 12 weeks.

Group Type: PLACEBO_COMPARATOR

matching liraglutide-placebo pre-filled pens

Intervention Type: DRUG

Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).

Interventions

Liraglutide Pen Injector [Victoza]

Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).

Intervention Type: DRUG

matching liraglutide-placebo pre-filled pens

Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• T2DM as defined by American Diabetes Association (ADA) criteria
• Adult patients with T2DM who are indicated to receive liraglutide, not as first-line therapy, in addition to diet and exercise to improve glycemic control
• Hemoglobin A1c (HbA1c) ≤ 9%
• Age ≥ 18 years old
• Body mass index (BMI) ≥ 27 Kg/m2 and/or waist circumference ≥ 102 cm (40 inches) in men and 88 cm (35 inches) in women, respectively.
• Clinically and angiographically stable CAD who requires CABG as part of the standard medical care, as CAD does not represent a contraindication for using liraglutide. The stability of the CAD further warranties that study patients will not be exposed to higher risk by using liraglutide

Exclusion Criteria

• Patients with a personal or family history of medullary thyroid carcinoma or patients with Multiple Endocrine Neoplasia syndrome type 2
• Patients with a prior serious hypersensitivity reaction to liraglutide
• Other contra-indications to liraglutide in accordance with risks and safety information included in the latest updated prescribing information
• Type 1 diabetes, as defined by ADA criteria
• Current use of other GLP-1A, dipeptidyl peptidase 4 (DPP4) or Sodium Glucose transporters 2 (SGLT2) inhibitors, thiazolidinediones (TZDs), pramlintide and fixed prandial insulin.
• Patients with unstable CAD, assessed by the Cardiology team and defined as new onset angina, rest angina, rapidly increasing or crescendo angina
• History of diabetic ketoacidosis, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy; acute or chronic infective diseases, cancer or chemotherapy, history of pulmonary, renal or liver diseases, and drug abuse
• Patients with chronic and acute inflammatory conditions such as sepsis, rheumatoid arthritis, ectopic dermatitis, asthma, ulcerative colitis.
• Current use of systemic corticosteroids in the 3 months prior this study.
• Pregnant or breast-feeding women
• Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Gianluca Iacobellis

Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gianluca Iacobellis, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

20170684

Identifier Type: -

Identifier Source: org_study_id