This trial demonstrated a significant 25% reduction in the primary composite outcome (HR, 0.75; 95% CI, CPI 455 0.65C0.86). Type 2 diabetes Abstract Results from cardiovascular outcome trials (CVOT) with 5 different sodium-glucose co-transporter 2 inhibitors (SGLT2i; empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin), initially developed for their glucose-lowering effect by blocking tubular glucose reabsorption in kidney, have been shown to decrease the risk of heart failure hospitalization (HFH) across a range of patients with and without atherosclerotic Rabbit polyclonal to Adducin alpha cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Following these CVOT results, SGLT2i (dapagliflozin, empagliflozin, sotagliflozin) also were reported to reduce HFH and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of existence or absence of T2DM. Ongoing studies have been conducted to evaluate the clinical benefit of SGLT2i (empagliflozin, dapagliflozin) in patients with heart failure with preserved ejection fraction (HFpEF). Although SGLT2i brought us to the entrance CPI 455 of a new era for prevention of HF incidence and worsening of HF, the search for pivotal mechanism of SGLT2i to improve our pharmacological armamentarium should continue in order to protect every HF patient CPI 455 from fatal progression of HF disease. In this review, we summarized the updated clinical evidences on SGLT2i (rather than basic and translational evidence) for reduction of HF risk in T2DM patients and favorable clinical outcomes in both HFrEF and HFpEF patients. INTRODUCTION Sodium-glucose co-transporter (SGLT) is a membrane protein that supplies sodium ions (Na+) and glucose like as glucose transporter. In human, there are 6 types of SGLT and, among which SGLT1 and SGLT2 are known to be involved in glucose resorption in the intestinal mucosa (mainly for SGLT1) or proximal tubule of the renal nephron (mainly for SGLT2).1) SGLT1 is mainly located in the small intestine and plays an important role in the absorption of galactose, in addition to glucose. SGLT2 is primarily distributed in the kidney and is responsible for 90% of renal glucose resorption.2) Under physiological conditions, 180 g of glucose are filtered and completely reabsorbed by the renal tubules. In diabetic patients, glucose can be found in the urine when hyperglycemia.3) Whereas SGLT1 transports 2 Na+ per one molecule of glucose and SGLT2 transports 1 Na+, SGLT2 can co-localize with the renal Na+/hydrogen exchanger (NHE3), responsible for Na+ reabsorption in the proximal tubule.4) SGLT2 inhibitors (SGLT2i) may cross-react with this NHE3 so inhibit Na+ reabsorption and increase natriuresis. In general, the glucose-lowering ability of SGLT2i through urinary glucose excretion can decrease hemoglobin A1c modestly (from 0.5% to 1 1.0%) in patients with diabetes. The glucosuric effect of SGLT2i depends on the blood glucose concentration. So hypoglycemia risk following SGLT2i use is low compared to other glucose-lowering drugs. Patients with type 2 diabetes mellitus (T2DM) are at high risk of heart failure (HF), about 20C30% found in diabetes clinical practice and had higher rates of heart failure hospitalization (HFH) with higher mortality.5) SGLT2i exert consistent favorable effects on the HFH across all trials.6) However, these drugs have inconsistent results on mortality. CPI 455 Depending on the trial, empagliflozin reduced the risk of cardiovascular (CV) death by 38% but by only 2% in the trial with dapagliflozin in T2DM.7),8) Not only are patients with T2DM at higher risk for HF, patients with HF are also at high risk for recurrent HFH, high CV mortality, and worsening of renal function with poor CPI 455 quality of life. The combined risk of HFH or CV death in patients with heart failure with reduced ejection fraction (HFrEF), was reduced by 25% with dapagliflozin or empagliflozin, mainly driven by a reduction of HFH.9),10) These benefits of SGLT2i relatively on short-term follow-up.