Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on several cardiometabolic biomarkers, but this is not sufficient to fully explain the significant reduction in cardiovascular risk and mortality reported with SGLT2 inhibitor treatment in patients with diabetes mellitus. The 8-week, randomized, open-label SHIFT-J study investigated the effects of adding canagliflozin vs intensified antihyperglycemic therapy on nocturnal home blood pressure (BP) in patients with poorly controlled type 2 diabetes and nocturnal BP on existing therapy. Patients were randomized to oral canagliflozin 100 mg/d or control (increased hypoglycemic dosage/addition of another hypoglycemic agent). The efficacy analysis included 78 patients (mean 69 years; 59% male). Nocturnal home systolic BP [HSBP] decreased by 5.23 mm Hg in the canagliflozin group and by 1.04 mm Hg in the control group (P = 0.078 for between-group difference in change from baseline to week 8 [primary endpoint]); corresponding decreases in HSBP from baseline to week 4 were 5.08 and 1.38 mm Hg, respectively (P = 0.054). Reductions in morning HSBP from baseline to week 4 (-6.82 mm Hg vs -1.26 mm Hg, P = 0.038) and evening HSBP from baseline to week 8 (-8.74 mm Hg vs -2.36 mm Hg, P = 0.012) were greater in the canagliflozin group than in the control group. Body mass index (P < 0.001) and N-terminal pro B-type natriuretic peptide level (NT-proBNP; P = 0.023) decreased more in the canagliflozin group than in the control group. Glycemic control improved comparably in both groups. Reduction of HSBP and NT-proBNP level may be potential mechanism by which SGLT2 inhibitors reduce cardiovascular event risk.