Abstract
Background: The risk of cardiovascular disease and mortality in salt-sensitive patients with diabetes mellitus and uncontrolled nocturnal hypertension is high. The SGLT2 inhibitor and ARB Combination theRapy in pAtients with diabetes and uncontrolled nocturnal hypertension (SACRA) study investigated changes in blood pressure (BP) with empagliflozin plus existing antihypertensive therapy.Methods: This multicenter, double-blind, parallel study was conducted in Japan. Adult patients with type 2 diabetes mellitus and uncontrolled nocturnal hypertension receiving stable antihypertensive therapy including angiotensin receptor blockers were randomized to 12 weeks' treatment with empagliflozin 10 mg once daily or placebo. Clinic BP was measured at baseline, and weeks 4, 8 and 12; 24-hour ambulatory BP monitoring (ABPM) was performed at baseline and week 12; and morning home BP was determined for 5 days before each visit. Primary efficacy end point was change from baseline in nighttime BP (ABPM).Results: 132 non-obese, older patients with well-controlled blood glucose were randomized (mean age 70 years, mean body mass index 26 kg/m2). Empagliflozin, but not placebo, significantly reduced nighttime systolic BP versus baseline (-6.3 mmHg; p=0.004); between-group difference in change from baseline -4.3 mmHg (p=0.159). Reductions in daytime, 24-hour, morning home and clinic systolic BP at 12 weeks with empagliflozin were significantly greater than with placebo (-9.5, -7.7, -7.5 and -8.6 mmHg, respectively; all p≤0.002). Between-group differences in body weight and glycosylated hemoglobin reductions were significant, but small (-1.3 kg and -0.33%; both p<0.001). At 4-weeks, amino terminal pro-B-type natriuretic peptide levels were reduced to a greater extent in the empagliflozin versus placebo group (-12.1%; p=0.013); atrial natriuretic peptide levels decreased with empagliflozin versus placebo at weeks 4 and 12 (-8.2% [p=0.008] and -9.7% [p=0.019]). Changes in antihypertensive medication during the study did not differ significantly between groups.Conclusions: Non-severely obese older diabetes patients with uncontrolled nocturnal hypertension showed significant BP reductions without marked reductions in glucose with the addition of empagliflozin to existing antihypertensive and antidiabetic therapy. Use of SGLT2 inhibitors in specific groups (e.g. those with nocturnal hypertension, diabetes, and high salt sensitivity) could help reduce the risk of heart failure and cardiovascular mortality.Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT03050229. [ABSTRACT FROM AUTHOR]