Blood Pressure Effects of SGLT2 Inhibitors: Mechanisms and Clinical Evidence in Different Populations.

PURPOSE OF REVIEW: Sodium glucose transporter 2 inhibitors (SGLT2 inhibitors) are increasingly prescribed due to their considerable benefits on clinical outcomes in people with diabetes, heart failure, and chronic kidney disease (CKD). Hypertension is a common comorbidity in each of these disease states, increasing risk of cardiovascular morbidity and mortality. We herein review the effects of SGLT2 inhibitors on blood pressure in different populations, proposed mechanisms of action, and the contribution of blood pressure lowering to end-organ protection. RECENT FINDINGS: A recognised effect of SGLT2 inhibitors in recent clinical trials is blood pressure lowering, with multiple postulated mechanisms. This advantageous effect was first identified in populations with type 2 diabetes mellitus, prior to expansion of these trials to broader cohorts. On our review, we identified that the blood pressure lowering effect of SGLT2 inhibitors appears to be a dose-independent class-effect, with a magnitude of effect comparable to that seen with a low dose hydrochlorothiazide. There is considerable evidence demonstrating that this effect is observed across populations including those with type 2 diabetes mellitus, chronic kidney disease, and resistant hypertension.

Expansion of phenotype of DDX3X syndrome: six new cases.

Pathogenic variants in DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder. Common facial dysmorphism within the cohort include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high arched palate, thin upper vermillion and smooth philtrum. Novel clinical features identified from this cohort include facial dysmorphisms, perinatal complications, valgus feet deformity, lipoatrophy, dystonic episodes, and cutaneous mastocytosis. This case series attempts to expand the phenotype of the DDX3X syndrome; however, it remains heterogeneous. Description of further cases is required to more accurately identify the significance of novel phenotypes within this cohort.