Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are cardioprotective drugs. We investigated their effects on left atrial function, a major determinant of cardiac diastolic dysfunction in type 2 diabetes mellitus. We also explored the association of changes in arterial stiffness with those of the LA strain after treatment. Materials and Methods: A total of 200 patients (59.5 ± 9.1 year old, 151 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n = 50 served as controls), liraglutide (n = 50), empagliflozin (n = 50) or their combination (liraglutide + empagliflozin) (n = 50). We measured at baseline and 6 months post-treatment: (a) left atrial and global left ventricular longitudinal strain by speckle tracking echocardiography; (b) pulse wave velocity (PWV) and central systolic blood pressure. Results: At baseline, there was a correlation of the LA reservoir strain with PWV (r = −0.209, p = 0.008), central SBP (r = −0.151, p = 0.030), EF (r = 0.214, p = 0.004) and GLS (r = −0.279, p = 0.009). The LA reservoir change 6 months post-treatment was correlated with the PWV change in all groups (r = −0.242, p = 0.028). The LA reservoir change 6 months post-treatment was correlated with the GLS change in all groups (r = −0.322, p = 0.004). Six months after intervention, patients treated with liraglutide, empagliflozin and their combination improved the left atrial reservoir strain (GLP1RA 30.7 ± 9.3 vs. 33.9 ± 9.7%, p = 0.011, SGLT2i 30 ± 8.3 vs. 32.3 ± 7.3%, p = 0.04, GLP1&SGLT2i 29.1 ± 8.7 vs. 31.3 ± 8.2, p = 0.007) compared to those treated with insulin (33 ± 8.3% vs. 32.8 ± 7.4, p = 0.829). Also, patients treated with liraglutide and the combination liraglutide and empagliflozin had improved left atrial conduction strain (p < 0.05). Empagliflozin or the combination liraglutide and empagliflozin showed a greater decrease of PWV and central and brachial systolic blood pressure than insulin or GLP-1RA. (p < 0.05). Conclusions: Impaired aortic elastic properties are associated with a decreased LA strain in type 2 diabetics. Treatment with liraglutide, empagliflozin and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with the improvement of arterial and myocardial functions.

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (−11.8% vs. −4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (−14% vs. −10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness.