Evolution of myocardial steatosis in high cardiovascular risk T2DM patients treated by GLP1 receptor agonists: LICAS study

Background

We hypothesized that the reduction of intramyocardial fat content may be involved in the cardioprotective effect of glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2D). Therefore, we aimed to evaluate the change in intramyocardial triglyceride content in T2D patients treated with GLP1-RA.

Methods

This monocentric proof-of-concept cohort study included patients with unbalanced T2D prior to the introduction of GLP1-RA. Patients underwent cardiac magnetic resonance imaging (MRI) coupled with nuclear magnetic resonance (NMR) spectroscopy at baseline and six months after the introduction (M6) of a GLP1-RA to assess changes in intramyocardial triglyceride levels and morphological, functional, and cardiac tissue parameters. The relative delta (Δ_r) between baseline and M6 was calculated and analyzed by Student test or sign test.

Results

Twenty-six patients (mean age = 62.2 ± 6.7 years, median HbA1c = 9.1 %) fulfilled inclusion criteria and had both NMR measures. Compared with baseline, relative intramyocardial triglyceride levels significantly decreased after six months of treatment (mean Δ_r = -26 % [95 %CI:-39; −13]p = 0.003), as well as glycated hemoglobin (HbA1c) (median Δ_r = -26 % [IQR:25], p < 0.0001), body mass index (BMI) (mean Δ_r = -6% [-9; −4], p < 0.0001) and left ventricular mass (mean Δ_r = -6 [-12; −1] p = 0.02). The relative evolution of intramyocardial triglyceride content was not correlated with the relative evolution of HbA1c (r = 0.10) and BMI (r = -0.02).

Conclusions

We demonstrate a significant reduction in intramyocardial triglyceride content in patients with T2D after six months of treatment with GLP1-RA. The lack of correlation with reductions in HbA1c and BMI suggests a specific effect of GLP1-RA on myocardial steatosis, which might contribute to their previously demonstrated cardiovascular benefits.