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Sodium glucose transport inhibitors

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
Fumitaka Okajima, Tomoko Nagamine, Yuko Nakamura, Naomi Hattori, Hitoshi Sugihara, Naoya Emoto
The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor (SGLT2I) or the co-administration of SGLT2I and dipeptidyl peptidase-4 inhibitor (DPP-4I) to insulin therapy is not well known. Fifty-eight patients with type 2 diabetes, admitted for glycemic control, were randomized to basal-bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring (CGM) before discharge...
October 20, 2016: Journal of Diabetes Investigation
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
Rohit Kedia, Supriya Kulkarni, Meredith Ross, Vijay Shivaswamy
The dramatic rise in the prevalence of obesity and diabetes is associated with increased morbidity, mortality, and public health care costs worldwide. The need for new, effective, and long-lasting drugs is urgent. Recent research has focused on the role of the inhibitors of sodium- glucose co-transporter 2 (SGLT-2). Clinical trials have shown that SGLT-2 inhibitors have glycemic efficacy and weight-lowering potential. Dual drug therapy is a recommended therapy for patients with new-onset type 2 diabetes who need significant glycemic control...
2016: Patient Preference and Adherence
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
Markus Schlaich, Rosemary Elliott, Caroline Rudnicka, Vance Matthews
OBJECTIVE: Sympathetic nervous system activation is a common feature in various metabolic disorders such as obesity, metabolic syndrome, and type-2 diabetes. The sodium glucose co-transporter 2 (SGLT-2) mediates re-absorption of glucose from the renal proximal tubules. SGLT-2 inhibitors have attracted substantial attention due to their glucose and blood pressure lowering effects. Furthermore, the SGLT-2 inhibitor empagliflozin has recently been associated with improved cardiovascular outcomes in patients with type 2 diabetes...
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
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
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
Xin Mao, Ling-Fang Wu, Hai-Juan Zhao, Wen-Yi Liang, Wen-Jing Chen, Shu-Xian Han, Qi Qi, Ya-Ping Cui, Shi Li, Guang-Hui Yang, Yan-Yan Shao, Dan Zhu, Ru-Feng Wang, Yun You, Lan-Zhen Zhang
Objective. To investigate the absorption property of the representative hydrolyzable tannin, namely corilagin, and its hydrolysates gallic acid (GA) and ellagic acid (EA) from the Fructus Phyllanthi tannin fraction (PTF) in vitro. Methods. Caco-2 cells monolayer model was established. Influences of PTF on Caco-2 cells viability were detected with MTT assay. The transport across monolayers was examined for different time points, concentrations, and secretory directions. The inhibitors of P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), organic anion transporting polypeptide (OATP) and sodium/glucose cotransporter 1 (SGLT1), and tight junction modulators were used to study the transport mechanism...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
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
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
Wai-Lung Ng, Kit-Man Lau, Clara B-S Lau, Tony K M Shing
Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in diabetes patients. Reported herein is a short and convergent synthetic route towards some small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palladium-catalyzed arylation reaction. This synthetic strategy enabled the discovery of two highly selective and potent SGLT2 inhibitors, thereby paving the way towards the development of carbasugar SGLT2 inhibitors as potential antidiabetic/antitumor agents...
October 24, 2016: Angewandte Chemie
Herpreet Deol, Leoni Lekkakou, Ananth K Viswanath, Joseph M Pappachan
Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre...
September 30, 2016: Endocrine
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
Linda A Villani, Brennan K Smith, Katarina Marcinko, Rebecca J Ford, Lindsay A Broadfield, Alex E Green, Vanessa P Houde, Paola Muti, Theodoros Tsakiridis, Gregory R Steinberg
OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. METHODS: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase, and the p70S6 kinase were assessed...
October 2016: Molecular Metabolism
Amira Obeid, Mark Pucci, Una Martin, Wasim Hanif
Sodium glucose co-transporter 2 inhibitors lower blood pressure by osmotic diuresis and can be considered in diabetic patients with resistant hypertension.
September 2016: JRSM Open
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
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