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SGLT2 inhibitor

M Luconi, L Raimondi, A Di Franco, E Mannucci
BACKGROUND: The results of the EMPA-REG-OUTCOME trial on type 2 diabetic patients at high risk for prior cardiovascular events showed that empagliflozin produces a remarkable reduction in the rates of hospitalization for heart failure (35%), cardiovascular death (38%), and all-cause death (32%). This unexpected cardio-protective action cannot be accounted for by the improvement of "classical" cardiovascular risk factors. AIMS: This review aims at summarizing current knowledge on the cardiovascular action of SGLT2 inhibitors and discuss the different hypotheses formulated to explain the results of the EMPA-REG-OUTCOME-study...
September 10, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Hermann Koepsell
Orally applied SGLT2 (SLC5A2) inhibitors that enter the blood and decrease renal reabsorption of glucose have been approved as antidiabetic drugs. They decrease blood glucose levels, slightly reduce body weight and blood pressure, and decrease the risk for diabetic nephropathy. The SGLT2 inhibitor empagliflozin has been shown to reduce the risk of severe cardiac failure. This review summarizes knowledge about the functions of SGLT2 and the pathophysiology of type 2 diabetes (T2D) and diabetic follow-up diseases...
October 20, 2016: Pharmacology & Therapeutics
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
Bhavana Sosale, Aravind R Sosale, Prassanna M Kumar, Shashank R Joshi
BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...
September 2016: Journal of the Association of Physicians of India
Bhavana Sosale, Aravind Sosale, Arpandev Bhattacharyya
INTRODUCTION: Dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a promising drug approved for the treatment of type 2 diabetes mellitus (T2DM). However, its cost is an obstacle for use in developing countries like India. Thus, we aimed to analyse the impact on the cost of insulin therapy after adding dapagliflozin for patients using insulin in real-world clinical practice. METHODS: This retrospective chart review study included patients with uncontrolled T2DM previously on maximum doses of OADs and insulin therapy, initiated on dapagliflozin...
October 19, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Hideaki Kaneto, Atsushi Obata, Tomohiko Kimura, Masashi Shimoda, Seizo Okauchi, Naoki Shimo, Taka-Aki Matsuoka, Kohei Kaku
Type 2 diabetes mellitus is characterized by insulin resistance in various insulin target tissues such as the liver, adipose tissue and skeletal muscle, and insufficient insulin secretion from pancreatic β-cells. Sodium-glucose co-transporter 2 (SGLT2) inhibitors which are newly developed anti-diabetic agents decrease blood glucose levels by enhancing urinary glucose excretion and thereby function in an insulin-independent manner. SGLT2 inhibitors exert beneficial effects for the reduction of insulin resistance as well as for the preservation of pancreatic β-cell function...
October 18, 2016: Journal of Diabetes
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
Asadur Rahman, Yui Takeshige, Yoshihide Fujisawa, Hirofumi Hitomi, Daisuke Nakano, Akira Nishiyama
OBJECTIVE: Disrupted circadian rhythm of blood pressure is associated with cardiovascular events in metabolic syndrome and obesity. Experiments were conducted to examine the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on circadian rhythm of blood pressure in a genetic model of obese metabolic syndrome (SHR/NDmcr-cp (+/+) (SHRcp)) and salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. DESIGN AND METHOD: Luseogliflozin (10 mg/kg/day, p...
September 2016: Journal of Hypertension
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
Chang Hee Jung
Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder and is a major global public health problem with a rapidly increasing prevalence. Although a wide range of pharmacotherapy for glycemic control in T2DM is now available, management of T2DM remains complex and challenging. The kidneys contribute to glucose homeostasis primarily by the glucose reabsorption from the glomerular filtrate. The sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of antidiabetes agents that inhibit glucose absorption from the kidney tubule independent of insulin, offer a unique opportunity to improve outcomes for patient with T2DM...
September 2016: Journal of Hypertension
Resham Poudel
The kidneys maintain glucose homeostasis through its utilization, gluconeogenesis, and reabsorption. Glucose is freely filtered and reabsorbed in order to retain energy essential between meals. The amount of glucose reabsorbed by the kidneys is equivalent to the amount entering the filtration system. With a daily glomerular filtration rate of 180 L, approximately 180 g (180 L/day × 100 mg/dL) of glucose must be reabsorbed each day to maintain an average fasting plasma glucose concentration of 5.6 mmol/L (100 mg/dL)...
September 2016: Journal of Hypertension
Zaid Abassi, Jonatan Leor, Natalie Landa, Firas Younis, Kenneth Hollander, Eric Mayoux, Lea Rath-Wolfson, Talma Rosenthal
OBJECTIVE: Hypertension and Diabetes commonly coexist and have been implicated in deterioration of kidneys, heart and impairment of pancreas. Empagliflozin (Empa), a selective SGLT2 inhibitor, is a new agent for treatment of diabetes via enhancing glucosuria, independent of insulin resistance. This study evaluates Empa's prophylactic beneficial effect on glomerular, cardiac and pancreatic integrity, in CRDH animals. DESIGN AND METHOD: Cohen Rosenthal Diabetic Hypertensive rats (CRDH) were divided into 3 groups: A- Sugar diet (SD) + Empa, B-Sugar Diet + Veh, C-Regular Chow + Veh (Control)...
September 2016: Journal of Hypertension
Antonius Baartscheer, Cees A Schumacher, Rob C I Wüst, Jan W T Fiolet, Ger J M Stienen, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Empagliflozin (EMPA), an inhibitor of the renal sodium-glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na(+) ([Na(+)]c) and Ca(2+) ([Ca(2+)]c) concentrations and decreased mitochondrial Ca(2+) concentration ([Ca(2+)]m) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na(+)]c, [Ca(2+)]c and [Ca(2+)]m in cardiomyocytes...
October 17, 2016: Diabetologia
Vasilios Tsimihodimos, Theodosios D Filippatos, Sebastian Fillippas-Ntekouan, Moses S Elisaf
Sodium-glucose co-transporter 2 inhibitors (SGLT-2) inhibitors) represent a new class of antidiabetic drugs that act through the inhibition of glucose and sodium reabsorption at proximal tubules. It has been shown that tThese substances may exhibit renonephroprotective properties, since they expressed clinically as a prevention of the deterioration of the glomerular filtration rate and a reductionreduce in the degree of albuminuria in patients with established diabetes-associated kidney disease. In this review we present in detail the pathophysiologic mechanisms that have been recently implicated in the rennephroprotective properties of SGLT-2 inhibitors...
October 7, 2016: Current Vascular Pharmacology
André J Scheen
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis...
September 28, 2016: Diabetes Research and Clinical Practice
Katsunori Suzuki, Yurie Mitsuma, Takaaki Sato, Takumi Anraku, Mariko Hatta
BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) on insulin have poor glycemic control and require add-on therapy to reach target glucose values. Increased insulin doses or the addition of an oral antidiabetic drug (OAD) may improve glycemic control, but many patients fail to achieve target values. The aim of this study was to compare the treatment efficacy and safety of three different therapies in such patients. METHODS: T2DM outpatients with poor glycemic control (HbA1c ≥ 7...
November 2016: Journal of Clinical Medicine Research
Rong Qiu, Dainius Balis, George Capuano, John Xie, Gary Meininger
: Metformin is typically the first pharmacologic treatment recommended for type 2 diabetes mellitus (T2DM), but many patients do not achieve glycemic control with metformin alone and eventually require combination therapy with other agents. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background therapy that consisted of metformin alone or in combination with other antihyperglycemic agents (AHAs; e...
October 12, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
1. Several SGLT-2 inhibitors are in clinical use for the management of type 2 diabetes. The objectives of the current review were: a) to provide a comparative pharmacokinetics including absorption, distribution, metabolism and excretory (ADME) profiles of three SGLT2 inhibitors namely: sergliflozin, remogliflozin and ertugliflozin; b) to provide some perspectives on possible developmental issues. 2. Based on the t1/2 values observed in humans, the rank order of the three SGLT-2 inhibitors were ertugliflozin (16 h) > remogliflozin (2-4 h) >sergliflozin (1-1...
October 10, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Tory J Andrews, Robert D Cox, Christina Parker, James Kolb
BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days...
October 4, 2016: Journal of Emergency Medicine
Andrea Egger, Marius E Kraenzlin, Christian Meier
Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk...
October 5, 2016: Current Osteoporosis Reports
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