Dapagliflozin decreases ambulatory central blood pressure and pulse wave velocity in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

Abstract

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce the incidence of heart failure and death in patients with type-2 diabetes mellitus. Arterial stiffness is a prominent risk factor for heart failure and overall mortality. The aim of this study was to evaluate the effects of dapagliflozin on ambulatory brachial and central blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 diabetes mellitus. This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 diabetes mellitus on monotherapy or combination therapy with two of: metformin, sulphonylurea, DPP-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. Baseline demographic, clinical and laboratory parameters were similar in the two groups. During follow-up, 24-h brachial SBP/DBP (129.0 ± 12.6/77.3 ± 7.3 vs. 123.2 ± 12.4/75.1 ± 6.4 mmHg; P < 0.001/P = 0.008) and central SBP/DBP (117.4 ± 10.5/78.9 ± 7.3 vs. 113.3 ± 8.8/77.3 ± 6.5 mmHg; P = 0.002/P = 0.047) significantly decreased in dapagliflozin but not in the placebo group. Corresponding reductions of 24-h brachial SBP (-5.8 ± 9.5 vs. -0.1 ± 8.7, P = 0.005) and central SBP (-4.1 ± 8.0 vs. -0.7 ± 7.8; P = 0.046) were greater with dapagliflozin than placebo. Twenty-four-hour heart-rate adjusted augmentation index significantly decreased with dapagliflozin and insignificantly with placebo. Importantly, there was a significant difference in change of estimated 24-h PWV (-0.16 ± 0.32 vs. 0.02 ± 0.27; P = 0.007) favoring dapagliflozin. In generalized linear mixed models including 24-h brachial SBP as a random covariate, the adjusted marginal means of delta 24-h central SBP and delta 24-h PWV were not significantly different between-groups. Treatment with dapagliflozin significantly reduces ambulatory brachial and central BP levels and PWV in patients with type-2 diabetes mellitus. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.