Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy. Methods: This multicenter prospective study evaluates the changes in ABP after 12weeks of dapagliflozin 10mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25mL/min/1.73 m2. Primary endpoint was the change of nighttime systolic blood pressure (SBP). Changes of daytime SBP, prevalence of normal dipping (day/night SBP ratio <0.9) and changes in ABP patterns, that is, sustained uncontrolled hypertension (SUCH), white coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and controlled hypertension (CH) were secondary endpoints. Results: Eighty-three of 96 patients completed the study [age 68.7±8.9 years, 73.5% males, GFR 49±17mL/min/1.73 m2, median albuminuria: 0.18 (interquartile range 0.10-0.38) g/24h]. After 12weeks of dapagliflozin, nighttime SBP declined by -3.0mmHg (95% confidence interval -5.2/-0.8mmHg; P=.010) with an improvement of nighttime SBP goal (<110mmHg) from 18.0% to 27.0% (P<.001). Similarly, the prevalence of normal dipping increased (from 31.3% to 50.6%, P=.005). A decrease in daytime (-2.4mmHg; P=.046) and office (-7.9mmHg; P=.009) SBP was also found. The decline of ambulatory and office SBP was associated with increased prevalence of CH (from 6.0% to 18.0%) and significant improvement of SUCH, WUCH and MUCH (P=.009). Albuminuria decreased (P<.001), whereas eGFR did not change (P=.297). Urinary tract infection (4.2%) and acute kidney injury (3.6%) were the main causes of drop-out. Only one patient showed a drop of nighttime SBP below 90mmHg. Conclusions: Dapagliflozin is associated with improvement in circadian blood pressure rhythm with no major safety signal related to excessive blood pressure ...