The combination of dulaglutide and dapagliflozin improves arterial stiffness, endothelial glycocalyx and albuminuria vs DPP-4 inhibitors independently of glycemic control

Abstract

Abstract Background Studies in recent years have shown that dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), improve or prevent diabetic nephropathy and macrovascular complications in patients with type 2 diabetes mellitus (T2DM). Purpose The aim of this study is to determine whether the combination of dulaglutide and dapagliflozin exerts improves arterial stiffness, endothelial glycocalyx and albuminuria in T2DM compared to dipeptidyl-peptidase 4 inhibitors (DPP-4is). Methods Overall 37 patients with T2DM were included in our study. 21 patients were transitioned from DPP-4is to dulaglutide and dapagliflozin (treatment group) and were followed immediately prior (baseline) and 4 months after the initiation of treatment. 16 patients, matched for sex, age and glycemic control, remained on treatment with DPP-4is (control group). In each visit we measured a) Carotid-femoral PWV b) central systolic blood pressure (cSBP) c) perfused boundary region (PBR) of the sublingual arterial microvessels, d) urinary albumin-to-creatinine ratio (UACR), e) glycosylated hemoglobin (HbA1c). Results There were no statistically significant differences in cardiovascular markers, UACR and HbA1c at baseline (p>0.05). After 4 months, patients on dulaglutide and dapagliflozin combination improved HbA1c (7.9±1.5% vs 6.59±0.6%, p<0.001), PBR (2.3±0.3 vs. 2.1±0.2 μm, p<0.05), PWV (11.9±0.3.5 vs. 10.9±2.2m/s, p<0.05), cSBP (128.5±23.6 vs. 121.1±15.7 mmHg, p<0.05) and UACR (413.66±352.57 vs. 248.06±203.5 mg/g, p<0.001). There were no statistically significant differences in PBR (2.1±0.3 vs. 2.2±0.3 μm, p>0.05), PWV (10.7±3.4 vs. 12±3.3m/s, p>0.05), cSBP (125.4±21.2 vs. 127±20.1 mmHg, p>0.05) and UACR (240.8±103.6 vs. 204.9±119.6 mg/g), in the control group, despite a statistically significant improvement of HbA1c (8.2±1.9% vs 7.3±1.3%, p<0.01). Conclusions The combination of dulaglutide and dapagliflozin improves arterial stiffness, endothelial glycocalyx and albuminuria compared to DPP-4is in patients with T2DM. Funding Acknowledgement Type of funding sources: None.