Effect of canagliflozin on nocturnal home blood pressure in Japanese patients with type 2 diabetes mellitus: The SHIFT‐J study

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.

Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study

“…A number of beneficial cardiovascular effects of SGLT2 inhibitors have been investigated, including reductions in blood pressure (BP), 6,7 attenuation of the salt sensitivity of BP, 8 improvements in arterial stiffness, 9 and sympatholytic effects 8 . We recently demonstrated that SGLT2 inhibitors significantly reduced out‐of‐office BP determined using ambulatory or home BP monitoring compared with placebo or control in patients with type 2 diabetes and uncontrolled nocturnal hypertension (a salt‐sensitive hypertension phenotype) 10,11 …”

A multicenter clinical trial to assess the efficacy of the digital therapeutics for essential hypertension: Rationale and design of the HERB‐DH1 trial

“…During the follow‐up (Table 1), the following interventions will be prohibited due to their potential to affect BP: (a) antihypertensive medications except when indicated based on the ambulatory BP levels taken at 12 weeks after registration; (b) the use of application software that measures BP, stores measured BP data or aims to reduce BPs; (c) intake of any foods approved by the Consumer Affairs Agency as “food for specified health uses”; (d) use of medications or Chinese herbal medicines known to cause drug‐induced hypertension (eg, non‐steroidal anti‐inflammatory drugs, licorice, glucocorticoid, cyclosporine, erythropoietin, oral contraceptives, and sympathomimetic agents [topical product as ophthalmic solution or ointments are excluded]); and (e) use of sodium‐glucose transporter 2 inhibitors, which have been shown to lower home and ambulatory BPs 18,19 . Antihypertensive or other medications can be used after 12 weeks of randomization according to the JSH 2019 Guideline and the discretion of physicians 1 .…”

The HOPE Asia Network activity for “zero” cardiovascular events in Asia: Overview 2020

“…Another promising area is the use of drugs with natriuretic action, such as angiotensin receptor‐neprilysin inhibitors, sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, and mineralocorticoid receptor (MR) blockers. Furthermore, renal denervation is a new treatment approach that might be more effective in Asians, who have higher salt sensitivity and higher salt intake .…”