Improvement of left ventricular global longitudinal strain (LV GLS) after 6-months of GLP-1 RAs treatment in diabetes mellitus type 2
Authors: Basile P , Napoli G , Siena P , Raffaele N , Monitillo F , Santoro D , Carella M C , Mushtaq S , Baggiano A , Fazzari F , Fusini L , Forleo C , Ciccone M M , Pontone G , Guaricci A I 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Glucagone Like Peptide-1 Receptor Agonists (GLP-1RAs) are incretine-based glucose-lowering drugs widely used in the treatment of Diabetes Mellitus type 2 (DM2). Several cardiovascular outcomes trials demonstrated that GLP-1RAs are capable to induce a reduction of major adverse cardiovascular events (MACE) in DM2 patients with atherosclerotic cardiovascular diseases (ASCVD) or with high/very high cardiovascular (CV) risk. However, the direct effect of GLP1-RAs on cardiac function needs to be further explored.

Purpose
The aim of this study was the investigation of the effects of GLP-1RAs semaglutide or dulaglutide on cardiac systolic function in patients with DM2 and ASCVD or high/very high CV risk.

Methods
We conducted a proof-of-concept, observational, perspective, monocentric study by the enrollment of 22 patients treated with semaglutide or dulaglutide from December 2019 to March 2020 coming from the outpatient diabetology clinic in our hospital. Each patient underwent a transthoracic echocardiographic evaluation before the drug initiation, and then reassessed after a mean follow-up of 6 months by two cardiologists with experience in echocardiography. The examination was focused on the detection of the left ventricular ejection fraction (LVEF) and the left ventricular global longitudinal strain (LV GLS) with speckle tracking echocardiography (STE) (figure 1).

Results
Mean age of the sample was 65 ± 10 years, with a small prevalence of male sex (64% of cases). A huge number of patients had arterial hypertension (100%), dyslipidaemia (95%), family history of CV disease (91%), obesity (86%), smoking habit (68%) and two patients had a previous myocardial infarction (MI). Chronic Obstructive Pulmonary Disease (COPD) was the most frequent comorbidity (32% of cases). A mild LV concentric hypertrophy was highly represented [median interventricular septum 12 (IQR 1) mm]. No one had valvular diseases, except for minimum/mild tricuspid and mitral regurgitation. No relevant alterations were seen in the right cardiac sections. The LVEF was normal in the majority of patients, with a median value of 59% (IQR 7%). The mean LV GLS was slightly under the normal range (−18,0% ± 1,8%). After 6-months of treatment with semaglutide or dulaglutide, was documented a clinical and statistically significant improvement of LV GLS (mean difference −1,4% ± 1,1%; p&lt;0,001), with a mean value tending towards the normal range (19,5% ± 2,1%) (figure 2). No relevant changes were seen on the other echocardiographic parameters evaluated.

Conclusions
In this setting of patients, a subclinical LV dysfunction defined by a mild reduction of LV GLS is common and may evolve towards diabetic cardiomyopathy. Semaglutide or dulaglutide should be considered as antidiabetic drugs in order to improve the systolic function. Further studies with a larger sample size and longer follow-up are ongoing to confirm these preliminary results.