THE EFFECT OF DAPAGLIFLOZIN ON 24-HOUR BLOOD PRESSURE AND ARTERIAL STIFFNESS IN PATIENTS WITH TYPE-2 DIABETES MELLITUS: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

Abstract

Objective: Arterial hypertension is present in > 90% of patients and arterial stiffness is a prominent risk factor for heart failure and overall mortality in patients with type-2 diabetes mellitus (DM). Previous evidence suggests that sodium-glucose transporter 2 (SGLT-2) inhibitors can effectively manage hyperglycemia, but also reduce office blood pressure (BP) levels and the incidence of heart failure and death in these patients. The aim of this study is to evaluate the effects of dapagliflozin on ambulatory blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 DM. Design and method: This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 DM on monotherapy or combination therapy with two of: metformin, sulphonylurea, DDP-4 inhibitor, or insulin. Patients were randomized in a 1:1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end. Results: Baseline demographic, clinical and laboratory parameters were similar in the two groups (age 61.74 ± 6.73 vs 60.64 ± 9.35; p = 0.534). During follow-up, 24-hour brachial SBP decreased in the active (128.97 ± 12.57 vs 123.17 ± 12.35; p < 0.001) but was similar in the control group (128.95 ± 12.41 vs 128.86 ± 13.45; p = 0.942). 24-hour central SBP/DBP significantly decreased only in the dapagliflozin (117.41 ± 10.52/78.88 ± 7.25 vs 113.30 ± 8.75/77.25 ± 6.54; p = 0.002/p = 0.047) group. Corresponding reductions of 24-hour central SBP (-4.12 ± 8.00 vs -0.65 ± 7.77; p = 0.046) were greater with dapagliflozin than placebo. Aortic pulse pressure (PP) decreased only in the dapagliflozin group (38.53 ± 7.44 vs 36.05 ± 6.59 mmHg; p = 0.004). 24-hour heart-rate adjusted augmentation-index significantly decreased with dapagliflozin. Importantly, there was a significant difference in the change of 24-hour PWV (-0.16 ± 0.32 vs 0.02 ± 0.27; p = 0.007) favoring dapagliflozin. Conclusions: Treatment with dapagliflozin produce statistically significant and clinically meaningful reductions in 24-hour brachial and central BP levels and reduce PWV levels in type-2 diabetics. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.