Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance

Abstract

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Keywords: Cardiovascular magnetic resonance; Diabetic cardiomyopathy; GLP-1Ra; SGLT2i.

Fig. 1

Examples of CMR sequences used to evaluate cardiovascular effects of SGLT2i or GLP-1Ra. ECV: extracellular volume; MRS: magnetic resonance spectroscopy; LGE: late gadolinium enhancement; STIR-T2: Short-TI Inversion Recovery

Fig. 2

Summary of the effects of sodium-glucose cotransporter-2 inhibitors EPO: Erythropoietin. LV: left ventricular; RAAS: renin-angiotensin-aldosterone system;

Fig. 3

Summary of the effects of Glucagon-Like Peptide-1 receptor agonists