The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p<0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.