Liraglutide Effects on Epicardial Fat Inflammatory Genes
Status:
Recruiting
Trial end date:
2022-06-30
Target enrollment:
Participant gender:
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 4-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 4 weeks up to 12 weeks to avoid the confounding effect of weight loss on the study
outcomes. EAT samples will be collected during cardiac surgery and processed for analysis of
mRNA and protein expression of EAT inflammatory genes such as Tumor Necrosis Factor-alpha
(TNF-α) and Interleukin 6 (IL-6), and GLP-1R.