title: Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure.
abstract: Improvement in cardiovascular (CV) morbidity and mortality in the EMPA-REG OUTCOME study provides new insight into the therapeutic use of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Although SGLT2 inhibitors have several pleiotropic effects, the underlying mechanism responsible for their cardioprotective effects remains undetermined. In this regard, the absence of a nocturnal fall in blood pressure (BP), that is, non-dipping BP, is a common phenomenon in type 2 diabetes and has a crucial role in the pathogenesis of CV morbidity and mortality. In most clinical trials, SGLT2 inhibitors reduce both systolic BP (~3-5 mm Hg) and diastolic BP (~2 mm Hg) in patients with type 2 diabetes. In addition, recent clinical and animal studies have revealed that SGLT2 inhibitors enable the change in BP circadian rhythm from a non-dipper to a dipper type, which is possibly associated with the improvement in CV outcomes in patients with type 2 diabetes. In this review, recent data on the effect of SGLT2 inhibitors on the circadian rhythm of BP will be summarized. The possible underlying mechanisms responsible for the SGLT2 inhibitor-induced improvement in the circadian rhythm of BP will also be discussed.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Asadur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002940:Circadian Rhythm / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors