Rationale: In recent years sodium-glucose cotransporter-2 inhibitors (SGLT-2-in) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) demonstrated beneficial effects on long-term cardiovascular outcomes in people with type 2 diabetes mellitus (pwT2D). However, the mechanisms of these beneficial effects are not fully understood. Methods: In a monocentric, observational, pilot study, we investigated cardiovascular effects of GLP1-RA dulaglutide (1.5 mg/weekly) and SGLT2-in dapagliflozin (10 mg/daily) in pwT2D. The aims were to investigate before and 3 months after the start of therapy the endothelium-dependent vascular dilator function, assessed by Flow Mediated Dilation (FMD), the endothelium-independent vasodilator function after glyceryl trinitrate, Nitrate-Mediated Dilation (NMD), and the effects on cardiac autonomic function through Heart Rate Variability (HRV). We also investigated if glucose variability (GV) correlates with abnormalities in vascular and autonomic functions through continuous glucose monitoring. Results: We enrolled 24 subjects, 16 on SGLT2-in, 8 on GLP1-RA. Age and sex were similar (SGLT2-in 56.9±7.8 years and 70% males, GLP1-RA 56.1±7.7 and 68% males) but BMI was slightly higher in the GLP1-RA group (SGLT2-in 26.9±2.9 kg/m2 vs GLP1-RA 32.6±4.3 kg/m2). After 3 months no changes on FMD (SGLT2-in pre 5.85±2.4 vs post 4.23±4.2; GLP1-RA pre 4.28±0.9 vs post 4.01±1.5, p interaction=0.54), NMD (SGLT2-in pre 8.2±2.4 vs post 8.62±4.3; GLP1-RA pre 8.38±3.9 vs post 10.2±9.6, p interaction=0.53) were found and no differences in the changes of HRV variables were noticed. Significant correlations emerged between GV parameters and HRV variables, suggesting higher parasympathetic tone in patients with higher levels and variability of glucose blood levels. Conclusion: The short-term treatment with dapagliflozin or dulaglutide did not significantly impact arterial dilation or cardiac autonomic function. Significant effects obtained with longer periods of treatment should be investigated.