Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial.
Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium; Clinical Pharmacology Unit, CHU Liège, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be.
A J
AJ
Scheen
Division of Nephrology, Dialysis, Transplantation and Hypertension, Department of Medicine, CHU Liège (ULg-CHU), Liège, Belgium.
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P
Delanaye
D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors
Blood pressure; Empagliflozin; Hypertension; Kidney; SGLT2 inhibitor; Type 2 diabetes