Effects of dapagliflozin and dulaglutide on blood pressure and coronary flow in liver steatosis patients with type 2 diabetes

AIM: To investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on cardiovascular function and hepatic metabolism in patients with type 2 diabetes mellitus (T2DM) and metabolic-dysfunction associated steatotic liver disease (MASLD). METHODS: This is an unblinded real-world study using propensity score analysis of consecutive patients with T2DM and MASLD received either SGLT-2i (dapagliflozin; n = 21), GLP-1RA (dulaglutide; n = 21), or dipeptidyl peptidase-4 inhibitors (DPP-4i; n = 20). At baseline and after 12 months, we assessed the perfused boundary region (PBR) as a marker of glycocalyx thickness, peripheral and central systolic blood pressure (cSBP), pulse wave velocity (PWV), coronary flow reserve (CFR), left ventricular global longitudinal strain (GLS), controlled attenuation parameter (CAP), and liver stiffness (E). RESULTS: At 12 months, all patients had reduced glycosylated hemoglobin and body mass index compared to baseline (P < 0.001), as well as a significant reduction in cSBP, PBR, PWV, CAP, E, and increase in CFR and GLS (P < 0.01). The percentage decrease in peripheral and central SBP was related with the improvement in PBR, PWV, CFR, and GLS at 12 months (P < 0.01). Dulaglutide showed greater improvement in GLS (22.6% vs. 8.5%, vs. 5.9%, P = 0.015) and PBR (P = 0.037) than dapagliflozin and DDP-4i. Both dulaglutide and dapagliflozin showed a greater increase in CFR than DDP-4i post-treatment. The percentage reduction in CAP was associated with the decrease in PBR, PWV and with the increase in GLS (P < 0.05). CONCLUSION: Twelve-month treatment with either SGLT-2i or GLP-1RA improves central hemodynamics, coronary flow and reduces hepatic steatosis in T2DM individuals with MASLD.