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Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes: Cardiovascular and Kidney Effects, Potential Mechanisms and Clinical Applications.
Abstract Sodium glucose co-transporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin and canagliflozin, are now widely approved anti-hyperglycemic therapies. Due to their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more importantly are osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures (BP) by 4-6/1-2 mmHg, respectively, which may underlie cardiovascular and kidney benefits. SGLT2 inhibition is also associated with an acute, dose-dependent reduction in eGFR by ~5 ml/min/1.73m(2) and...
Source: Circulation - July 27, 2016 Category: Cardiology Authors: Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ Tags: Circulation Source Type: research

Novel antidiabetic drugs and cardiovascular risk: primum non nocere
Conclusions Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients.
Source: Nutrition, Metabolism and Cardiovascular Diseases - June 15, 2016 Category: Nutrition Source Type: research

Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials.
Abstract Sodium glucose cotransporter 2 (SGLT2) inhibitors have a unique mechanism of action leading to excretion of glucose in the urine and subsequent lowering of plasma glucose. This mechanism is independent of β-cell function; thus, these agents are effective treatment for type 2 diabetes mellitus (T2DM) at theoretically any disease stage. This class should not confer an additional risk of hypoglycemia (unless combined with insulin or an insulin secretagogue) and has the potential to be combined with other classes of glucose-lowering agents. Empagliflozin is one of three currently approved SGLT2 inhibitors in...
Source: Current Diabetes Reviews - June 12, 2016 Category: Endocrinology Authors: Levine MJ Tags: Curr Diabetes Rev Source Type: research

SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?
Abstract While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise. The...
Source: Diabetologia - June 10, 2016 Category: Endocrinology Source Type: research

EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.
Abstract During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease. In the majority of CV outcome studies, CV ris...
Source: Clinical Therapeutics - May 18, 2016 Category: Drugs & Pharmacology Authors: Schernthaner G, Schernthaner-Reiter MH, Schernthaner GH Tags: Clin Ther Source Type: research

SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study
Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%. This beneficial eff...
Source: Diabetes Care - April 20, 2016 Category: Endocrinology Authors: Abdul-Ghani, M.; Del Prato, S.; Chilton, R.; DeFronzo, R. A. Tags: Cardiovascular Disease and Diabetes Source Type: research

Empagliflozin Reduces Cardiovascular Events and Mortality in Type 2 Diabetes.
Authors: Guthrie R Abstract Review of: Zinnam, B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2015; 373: 2117-2128. Patients were required to have a history of established cardiovascular disease, along with Type 2 Diabetes but were either not on antidiabetic therapy for the preceding 12 weeks, with a glycated hemoglobin level between 7% and 9%, or were on stable antidiabetic therapy for the preceding 12 weeks, with a glycated hemoglobin between 7.0% and 10.0%. Patients were randomized in a 1:1:1 ratio to either empagliflozin ...
Source: Postgraduate Medicine - April 6, 2016 Category: Internal Medicine Tags: Postgrad Med Source Type: research

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis
Publication date: Available online 18 March 2016 Source:The Lancet Diabetes & Endocrinology Author(s): Jason H Y Wu, Celine Foote, Juuso Blomster, Tadashi Toyama, Vlado Perkovic, Johan Sundström, Bruce Neal Background In patients with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce glucose concentrations, blood pressure, and weight, but to increase LDL cholesterol and the incidence of urogenital infections. Protection against cardiovascular events has also been reported, as have possible increased risks of adverse outcomes such as ketoacidosis and bone fracture. We a...
Source: The Lancet Diabetes and Endocrinology - March 19, 2016 Category: Endocrinology Source Type: research

Sitagliptin and other 'gliptins'- why prescribe them?
Authors: Doggrell SA, Dimmitt SB Abstract INTRODUCTION: In 2008, the Federal Drug Administration (FDA) required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase (DPP)-4 inhibitors ('gliptins'). At present, there is contradictory evidence on whether the gliptins increase hospitalizations for heart failure. Areas covered: This is an evaluation of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in high risk cardiovascular subjects with type 2 diabetes [1]. TECOS demonstrated non-inferiority for sitagliptin over placebo for the primary ...
Source: Expert Opinion on Pharmacotherapy - February 14, 2016 Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

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