DOCSLIB.ORG

An Emerging Protagonist: Sodium Glucose Co-Transporters (Sglts)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Emerging Protagonist: Sodium Glucose Co-Transporters (Sglts) abetes & Di M f e o t a l b a o Ahmed et al., J Diabetes Metab 2014, 5:4 n l r i s u m o DOI: 10.4172/2155-6156.1000358 J Journal of Diabetes and Metabolism ISSN: 2155-6156 Review Article Open Access An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus Danish Ahmed1*, Manju Sharma2, Vikas Kumar1 and Yadav Pankajkumar Subhashchandra1 1Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences (SHIATS)-Deemed University, India 2Department of Pharmacology, JamiaHamdard University, Hamdard Nagar, New Delhi, India Abstract Contemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. Kidney emerges out as a novel and potential target to trim down the complications of T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which are present at the luminal surface cells that covers the first segment of proximal tubules. Competitive inhibition of SGLT2 therefore represents an innovative therapeutic strategy for the treatment of hyperglycaemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. SGLT2 inhibitors are coupled with osmotic dieresis and loss of weight which aid in reducing the blood pressure. The observation that individuals with familial renal glycosuria maintain normal long- term kidney function provides some encouragement that this mode of action will not adversely affect renal function. This novel mechanism of targeting kidney for the treatment of T2DM is reasonably valuable and is independent of insulin and clutch with the low risk of hypoglycemia. Keywords: SGLT2; Diabetes; Kidney; Hyperglycemia; Type 2 the concentration gradient. Sodium is the major ion present in the diabetes mellitus mammals whose gradient across the cell membrane has been used as thrust. The secondary active transport of sugars, carboxylic acid and the Abbreviations: SGLTs: Sodium-Dependent Glucose Cotransporters; aminoacids rivet the synchronized movement of sodium ions by and T2DM: Type2 Diabetes Mellitus; HbA1c: Glycated Heamoglobin ; large in the same direction as the substrate [6] (Figure 1). FPG: Fasting Plasma Glucose; HRQOL: Health Related Quality of Life; CFU: Colony Forming Units; OADs: Oral Antidiabetic Drugs Kidney is the main organ where active transport of sugar takes place in the early part of the proximal tubule. Research work on the Introduction transport of sugar in the early and late segments of proximal tubule and vesicles demonstrate that the kidney contains two D-glucose co- Diabetes has become an engorgement apprehension worldwide. transporters with the difference in their stoichiometry for sodium in More or less 285 million people all over the world will be suffering the early proximal tubule. There is a mutual translocation of one sugar from diabetes by the end of 2010. WHO estimates that more than 346 and one sodium molecule in the luminal membrane while two sodium million people worldwide have diabetes [1]. This number is likely to ions are transferred with one sugar molecule in the late part of proximal become more than double by 2030 without intervention. Almost 80% of tubule. There is a divergence in the affinity for D-glucose for the two diabetes deaths occur in low- and middle-income countries. The most transporters [7] (Figure 2). common disorder of glucose homeostasis is Type2 Diabetes Mellitus (T2DM). It accounts for 90-96% of all cases of diabetes [2]. Sodium- The transporter in the early part has been identified as SGLT1 at the Dependent Glucose Cotransporters (SGLTs) facilitate the transport of same time the transporter found in the early proximal tubule as SGLT2. glucose against a concentration gradient with synchronized transport The sodium gluocose co-transporter (SGLT2) is a high capacity, low of sodium down a concentration gradient [3]. The anticipation is affinity proximal tubular cell transporter that reabsorbs filtered glucose. that there is about 90% of total renal glucose reabsorption is aided Mutations in this transporter lead to renal glycosuria. In diabeticanimal by SGLT2. Thus a new therapeutic approach without dependence on models, there appears to be up-regulation of the SGLT2 receptors and insulin and appropriate for use in amalgamation with other agents would be preeminent choice for treatment of hyperglycemia in type 2 diabetes mellitus (T2DM). Sodium Glucose co-transporter inhibitors create a center of attention as there is a need of potential therapy for *Corresponding author: Danish Ahmed, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology diabetes mellitus with lesser side effects [4,5]. This review scrutinize the and Sciences (SHIATS)-Deemed University, Allahabad, Uttar Pradesh, India, niceties of various SGLT2 inhibitors Tel: 919580001578; Fax: 91 532 2684190; E-mail: [email protected] The role of SGLT is fundamental in the mutual transfer of sugar Received February 24, 2014; Accepted March 16, 2014; Published March 22, and sodium across the epithelial membrane. The transport of sugar 2014 takes place in the small intestine and the renal tubule through active Citation: Ahmed D, Sharma M, Kumar V, Pankajkumar Y, chandra S (2014) transport. It necessitates the coupling of cellular energy metabolism An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a to the transepithelial transfer. It is SGLT where the coupling takes Burgeoning Target for the Treatment of Diabetes Mellitus. J Diabetes Metab 5: 358 doi:10.4172/2155-6156.1000358 place. There is no hydrolysis of ATP is engaged as compared to the primary active transport episodes for instance those intervened by ion Copyright: © 2014 Ahmed D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted translocating ATPases. As an alternative the SGLT exploit the energy use, distribution, and reproduction in any medium, provided the original author and accumulated in an ion gradient for the translocation of sugars against source are credited. J Diabetes Metab ISSN: 2155-6156 JDM, an open access journal Volume 5 • Issue 4 • 1000358 Citation: Ahmed D, Sharma M, Kumar V, Pankajkumar Y, chandra S (2014) An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus. J Diabetes Metab 5: 358 doi:10.4172/2155-6156.1000358 Page 2 of 7 acquaintances pave the way for the identification of an identical gene in the kidney [9]. This further allowed the researchers to do mutagenesis Glucose Lumen studies, structural elucidation and the discovery of substrate binding Na+ Basolateral Membrane sites as well as inhibitor binding sites [8]. SGLT2 The extensive research on the membrane topology of the transporter S1 Proximal which was possible only after the acquaintance of the sequence was Tubule Na+ done. The research showed that the N-terminus of thee transporter Glucose is pointing outside of the cell with 14 transmembrane segments. K+ The position of the loop 13-14 is essential after pholrizin binding site requires the loop 13-14. The C-terminus also plays a vital role in the recognition and translocation of the sugar [8]. The N-terminal segments IV-V are implicated in the recognition of sodium as well as GLUT2 glucose binding (Table 1). K+ Blood Na+K+ATPase Pump Glucose Na+ Lateral Intercellular Space Pancreas Fat Cells Insulin Glucagon Insulin + - + Glomerulus Bowmans Capsule Distal Nephron Tubule Liver 90 mg/100 ml Skeletal Proximal Muscle Tubule Collecting Duet Loop of Henle Fasting Plasma Glucose Kidney Figure 2: Normal glucose homeostasis. This outlines the hormonal interactions that are important in regulating normal glucose homeostasis. Normal fasting glucose homeostasis involves the hormonal regulation of glucose utilization and production, as well as the filtration and reabsorption of glucose by the kidney10. Under basa conditions, Kidney glucose uptake by the tissues is matched by glucose production from the liver; this enables fine regulation of glucose at a fixed level. Gluconeogenesis in the liver helps prevent hypoglycaemia. (Reproduced with permission from Edward C. Chao, Copyright @2010, Macmilan Publishers Limited). Figure 1: Reabsorption of glucose from the renal proximal tubules by the sodium glucose cotransporters SGLT2. Almost all of the glucose entering glomeruli in the afferent glomerular arterioles Selectivity for UGE in humans at Reduction in is filtered into the nephron fluid of the proximal renal tubules. Most (up to Compound SGLT2 vs. SGLT1 highest dose; mean HbA1c (%) 90%) of this filtered glucose is reabsorbed in the initial proximal convoluted (Fold) value ± SDa (g/day) segment (S1) by SGLT2 located at the luminal surface of proximal tubular cells. 90.8 ± 16.0 [29] Remaining glucose is reabsorbed from the filtrate in themore distal convoluted ASP1941 255 [28] 58.9 ± 14.6 [31] −0.8 [30] and straight segments by SGLT1. Glucose within the proximal tubular cells is 50 [30] then transported back to the interstitial compartment and thence to the plasma by the facilitative glucose transporters GLUT2 in the S1 segment, respectively. 72.6 ± 35.9 [33] In normal individuals with an average plasma glucose concentration of 5-5.5 BI 10773 >2,500 [32] 88 ± 20.3 [34] NR mmol/L (90-100mg/dL), approximately 160–180 g of glucose is filtered daily, 90.8 [35] with less than 0.5 g/day of glucose appearing in the urine based on Bakris et 129.2 ± 20.8 SE [37] Canagliflozin 414 [36] −0.92 [37] al. and Bays. 113 [38] −0.61 to −0.89 Dapagliflozin 1,200 [39] 70 [22] [16-19] GLUT2mRNA.
Load more

Recommended publications
  • Valstybinės Vaistų Kontrolės Tarnybos Prie Lietuvos Respublikos Sveikatos Apsaugos Ministerijos Viršininko Įsakymas
    VALSTYBINĖS VAISTŲ KONTROLĖS TARNYBOS PRIE LIETUVOS RESPUBLIKOS SVEIKATOS APSAUGOS MINISTERIJOS VIRŠININKO ĮSAKYMAS DĖL VALSTYBINĖS VAISTŲ KONTROLĖS TARNYBOS PRIE LIETUVOS RESPUBLIKOS SVEIKATOS APSAUGOS MINISTERIJOS VIRŠININKO 2006 M. LAPKRIČIO 2 D. ĮSAKYMO NR. 1A-658 „DĖL TARPTAUTINIŲ PREKĖS ŽENKLU NEREGISTRUOTŲ VAISTINIŲ MEDŽIAGŲ PAVADINIMŲ ATITIKMENŲ LIETUVIŲ KALBA SĄRAŠO PATVIRTINIMO“ PAKEITIMO 2011 m. gegužės 5 d. Nr. 1A-416 Vilnius Atsižvelgdamas į Pasaulinės sveikatos organizacijos 2011 m. paskelbtą 65-ąjį Rekomenduojamų tarptautinių prekės ženklu neregistruotų vaistinių medžiagų pavadinimų (INN) sąrašą, p a k e i č i u Tarptautinių prekės ženklu neregistruotų vaistinių medžiagų pavadinimų atitikmenų lietuvių kalba sąrašą, patvirtintą Valstybinės vaistų kontrolės tarnybos prie Lietuvos Respublikos sveikatos apsaugos ministerijos viršininko 2006 m. lapkričio 2 d. įsakymu Nr. 1A-658 „Dėl Tarptautinių prekės ženklu neregistruotų vaistinių medžiagų pavadinimų atitikmenų lietuvių kalba sąrašo patvirtinimo“ (Žin., 2006, Nr. 119-4557; 2007, Nr. 13-519, Nr. 43-1672; 2008, Nr. 9- 330, Nr. 24-896; 2010, Nr. 152-7773): 1. Papildau nauja eilute, kurią po eilutės „Amtolmetin guacil Amtolmetinas guacilas Amtolmetinum guacilum“ išdėstau taip: „Amuvatinib Amuvatinibas Amuvatinibum“ 2. Papildau nauja eilute, kurią po eilutės „Anagestone Anagestonas Anagestonum“ išdėstau taip: „Anagliptin Anagliptinas Anagliptinum“ 3. Papildau nauja eilute, kurią po eilutės „Atazanavir Atazanaviras Atazanavirum“ išdėstau taip: „Atecegatran Atecegatranas Atecegatranum“
    [Show full text]
  • Natural Products As Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors
    Reviews Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors Author ABSTRACT Wolfgang Blaschek Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glu- Affiliation cose absorption, gluconeogenesis, biosynthesis and mobiliza- Formerly: Institute of Pharmacy, Department of Pharmaceu- tion of glycogen, glucose consumption in all tissues and glo- tical Biology, Christian-Albrechts-University of Kiel, Kiel, merular filtration, and reabsorption of glucose in the kidneys. Germany Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the Key words family of facilitative glucose transporters (GLUTs) or to the Malus domestica, Rosaceae, Phlorizin, flavonoids, family of sodium glucose cotransporters (SGLTs). The intesti- ‑ SGLT inhibitors, gliflozins, diabetes nal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the received February 9, 2017 kidney SGLT2 and SGLT1 are responsible for reabsorption of revised March 3, 2017 filtered glucose from the primary urine, and GLUT2 and accepted March 6, 2017 GLUT1 enable the transport of glucose from epithelial cells Bibliography back into the blood stream. DOI http://dx.doi.org/10.1055/s-0043-106050 The flavonoid phlorizin was isolated from the bark of apple Published online April 10, 2017 | Planta Med 2017; 83: 985– trees and shown to cause glucosuria. Phlorizin is an inhibitor 993 © Georg Thieme Verlag KG Stuttgart · New York | of SGLT1 and SGLT2. With phlorizin as lead compound, specif- ISSN 0032‑0943 ic inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of Correspondence type 2 diabetes.
    [Show full text]
  • Remogliflozin Etabonate, a Selective Inhibitor of the Sodium-Glucose
    Clinical Care/Education/Nutrition/Psychosocial Research BRIEF REPORT Remogliflozin Etabonate, a Selective Inhibitor of the Sodium-Glucose Transporter 2, Improves Serum Glucose Profiles in Type 1 Diabetes 1,2 3 SUNDER MUDALIAR, MD JUNE YE, PHD placebo (placebo), 2) mealtime insulin 1 3 DEBRA A. ARMSTRONG, BA, RN, CCRC ELIZABETH K. HUSSEY, PHARMD 2 3 injection + RE placebo (prandial insulin), ANNIE A. MAVIAN, MD DEREK J. NUNEZ, MD 3 3 1,2 ) placebo insulin injection + 50 mg RE (RE ROBIN O’CONNOR-SEMMES, PHD ROBERT R. HENRY, MD 3 3 50 mg), 4) placebo insulin injection + 150 PATRICIA K. MYDLOW, BS ROBERT L. DOBBINS, MD, PHD mg RE (RE 150 mg), and 5) placebo insulin injection + 500 mg RE (RE 500 mg). d fl Each individual received 75-g oral OBJECTIVES Remogli ozin etabonate (RE), an inhibitor of the sodium-glucose transporter glucose and identical meals during all 2, improves glucose profiles in type 2 diabetes. This study assessed safety, tolerability, pharma- cokinetics, and pharmacodynamics of RE in subjects with type 1 diabetes. treatment periods. Frequent samples were obtained for measurement of plasma RESEARCH DESIGN AND METHODSdTen subjects managed with continuous sub- glucose and insulin concentrations. Urine cutaneous insulin infusion were enrolled. In addition to basal insulin, subjects received five samples were collected for 24 h to assess randomized treatments: placebo, prandial insulin, 50 mg RE, 150 mg RE, and mg RE 500. creatinine clearance and glucose excre- d tion. Plasma samples were collected for RESULTS Adverse events and incidence of hypoglycemia with RE did not differ from placebo fl and prandial insulin groups.
    [Show full text]
  • A Review on Evolution in Triglyceride Determination
    Available online at www.derpharmachemica.com ISSN 0975-413X Der Pharma Chemica, 2018, 10(5): 84-88 CODEN (USA): PCHHAX (http://www.derpharmachemica.com/archive.html) Sodium-glucose co-transporter 2 (SGLT2) Inhibitors: New Target for Type 2 Diabetes Mellitus (T2DM) Review Swapna Vadlamani* Asst. proffesor, NIPER, Hyderabad, Andhra Pradesh, India ABSTRACT Introduction: Knocking out type2 diabetes by new insulin independent renal glucose transporters as targets, reducing the side effects related to high rise in glucose levels is a more efficient way to manage diabetes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors block reabsorption of glucose back into the blood and stimulate secretion in urine in a way controlling blood glucose levels. Areas discussed: We emphasize in this review an overview of type 2 diabetes. New insulin independent targets, SGLT family inhibitors and their mechanism of action are briefly discussed. Molecular modeling studies carried out for new analogues of SGLT2 were indicated and also about current marketed SGLT drugs their safety issues are briefly outlined. Conclusion: SGLT2 inhibitors are very promising drugs for near future, where insulin sensitization is a problem. A combination of drugs related to insulin dependent pathway and also independent pathway like SGLT2/SGLT1 drugs will be more effective in glycemic control with lesser side effects. Keywords: Type II Diabetes, SGLT2 inhibitors INTRODUCTION Present scenario of food habits and absolutely very less physical activity is becoming the major cause for obesity finally leading to diabetes. Diabetes is said to be a rich man disease and mostly occurs at the later age of 40, but now one in every 5 persons at early age diagnosed turned to be diabetic mainly because of lifestyle changes.
    [Show full text]
  • Exploring Glycosuria As a Mechanism for Weight and Fat Mass Reduction. a Pilot Study with Remogliflozin Etabonate and Sergliflozin Etabonate in Healthy Obese Subjects
    Journal of Clinical & Translational Endocrinology 1 (2014) e3ee8 Contents lists available at ScienceDirect Journal of Clinical & Translational Endocrinology journal homepage: www.elsevier.com/locate/jcte Research Paper Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects Antonella Napolitano a,*, Sam Miller a, Peter R. Murgatroyd c, Elizabeth Hussey b, Robert L. Dobbins b, Edward T. Bullmore a, Derek J.R. Nunez b View metadata, citation and similar papers at core.ac.uk brought to you by CORE a Clinical Unit in Cambridge, GlaxoSmithKline, Addenbrookes Hospital, Cambridge, UK b Metabolic Pathways and Cardiovascular Unit, GlaxoSmithKline,provided by NC, Elsevier USA - Publisher Connector c Wellcome Trust Clinical Research Facility, Cambridge University Hospital NHS Trust, UK article info abstract Article history: Inhibitors of sodium-dependent glucose co-transporter 2 (SGLT2) increase glucose excretion in the urine Received 16 October 2013 and improve blood glucose in Type 2 diabetes mellitus. Glycosuria provides an energy and osmotic drain Received in revised form that could alter body composition. We therefore conducted a pilot study comparing the effects on body 26 November 2013 composition of two SGLT2 inhibitors, remogliflozin etabonate (RE) 250 mg TID (n ¼ 9) and sergliflozin Accepted 5 December 2013 etabonate (SE) (1000 mg TID) (n ¼ 9), with placebo (n ¼ 12) in obese non-diabetic subjects. Both drugs Available online 7 February 2014 were well tolerated during 8 weeks of dosing, and the most common adverse event was headache. No urinary tract infections were observed, but there was one case of vaginal candidiasis in the RE group.
    [Show full text]
  • PKB XXVI 2018 Pendidikan Kedokteran Berkelanjutan (PKB) XXVI Ilmu Penyakit Dalam FK UNUD/RSUP Sanglah 2018
    PKB XXVI 2018 Pendidikan Kedokteran Berkelanjutan (PKB) XXVI Ilmu Penyakit Dalam FK UNUD/RSUP Sanglah 2018 “Controversies in Internal Medicine” PROCEEDING BOOK Prime Plaza Hotel- Gedung Angsoka Lantai 4 RSUP Sanglah Denpasar 1-3 November 2018 EDITORS : Prof. DR. dr. I Made Bakta, Sp.PD-KHOM, FINASIM Prof. DR. dr. I Dewa Nyoman Wibawa, Sp.PD-KGEH, FINASIM Prof. DR. dr. Ketut Suastika, SpPD-KEMD Prof. DR. dr. Tjok Raka Putra, SpPD-KR Prof. DR. dr. K Tuti Parwati, SpPD-KPTI Prof. DR. dr. IB Ngurah Rai, SpP (K) Prof. DR. dr. Gde Raka Widiana, SpPD-KGH DR. dr. Tuty Kuswardani, SpPD-KGer, MARS DR. dr. K Rina, SpPD, SpJP UDAYANA UNIVERSITY PRESS DAFTAR ISI KATA PENGANTAR i KONTRIBUTOR ii DAFTAR ISI viii JADWAL ACARA xiv MATERI SYMPOSIUM CONTROVERSIES IN MEDICINE: CHALLENGES AND 1 OPPORTUNITIES I Made Bakta GOAL ORIENTED IN HYPERTENSION: UNDER CONTROL 11 WITH SINGLE PILL COMBINATION: AMLODIPINE/ VALSARTAN I Wayan Sudhana CURRENT CONCEPTS IN CHRONIC HEPATITIS B 19 TREATMENT I D N Wibawa ANTIVIRAL THERAPY: SHOULD IT BE LIFELONG? 28 I G A Suryadharma ROLE OF KIDNEY IN GLUCOSE HOMEOSTASIS 31 I Gde Raka Widiana viii LINKING TYPE 2 DIABETES MEDICATION WITH 58 CARDIOVASCULAR OUTCOME Ketut Suastika DIAGNOSTIC MODALITY FOR LUNG TUBERCULOSIS 72 I Made Bagiada ROLE OF IGRA IN DIAGNOSIS OF LUNG TUBERCULOSIS 88 Elva Aprilia Nasution CONTROVERSION OF PHARMACOLOGIC THERAPY FOR 89 ANOREXIA IN ELDERLY Tuty Kuswardhani CHOOSING AMINO ACIDS FOR TREATING SARCOPENIA 106 IN ELDERLY: WHICH ONE IS BETTER? I G P Suka Aryana OVERVIEW OF OSTOEOARTHRITIS 113 Tjokorda Raka
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • Reniva Monograph
    Product Monograph Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION 1 SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT 1 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 3. PHARMACEUTICAL FORM 1 4. CLINICAL PARTICULARS 1 4.1 Therapeutic indications 1 4.2 Posology and Method of Administration 1 4.3 Contraindications 2 4.4 Special Warnings and Precautions for Use 2 4.5 Interaction with other medicinal products and other forms of interactions 3 4.6 Fertility, pregnancy and lactation 4 4.7 Effects on ability to drive and use machines 5 4.8 Undesirable effects 5 4.9 Overdose 8 5. PHARMACOLOGICAL PROPERTIES 8 5.1 Pharmacodynamic properties 8 5.2 Pharmacokinetic properties 10 6. PHARMACEUTICAL PARTICULARS 11 6.1 List of excipients 11 6.2 Incompatibilities 11 6.3 Shelf Life 11 6.4 Special Precautions for Storage 11 6.5 Nature and Contents of the Container 11 PART II: SCIENTIFIC INFORMATION 12 1. PHARMACEUTICAL INFORMATION 12 2. CLINICAL TRIALS 12 2.1. Clinical Studies and designs 13 2.2. Study Results 16 3. DETAILED PHARMACOLOGY 20 4. TOXICOLOGY 34 5. REFERENCES 38 PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY OF PRODUCT CHARACTERISTICS Remogliflozin etabonate 100 mg Tablets 1. NAME OF THE MEDICINAL PRODUCT Remogliflozin etabonate 100 mg Tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Remogliflozin etabonate 100 mg Tablets Each film coated tablet contains: Remogliflozin Etabonate …. 100 mg Excipients q.s Colour: Titanium Dioxide USP. 3. PHARMACEUTICAL FORM Film coated tablets 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Remogliflozin etabonate is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycemic control as: • Monotherapy when diet and exercise alone do not provide adequate glycaemic control.
    [Show full text]
  • Impact of the 8-Week Administration of Tofogliflozin for Glycemic Control and Body Composition in Japanese Patients with Type 2 Diabetes Mellitus
    □ ORIGINAL ARTICLE □ Impact of the 8-week Administration of Tofogliflozin for Glycemic Control and Body Composition in Japanese Patients with Type 2 Diabetes Mellitus Sachie Hirose 1, Shinsuke Nakajima 2, Yasuyuki Iwahashi 1, Akane Seo 1, Tetsuya Takahashi 1 and Yoshikazu Tamori 1,2 Abstract Objective The adverse effects of selective sodium-glucose co-transporter 2 (SGLT2) inhibitors generally ap- pear within about two or three months after treatment initiation in Japan. Therefore, we investigated the im- pact of tofogliflozin, a class of SGLT2 inhibitors, on glycemic control and body composition during this pe- riod in Japanese patients with type 2 diabetes mellitus. Methods This single-arm open-label study enrolled 20 patients. Patients received tofogliflozin 20 mg once daily for 8 weeks. At week 8, changes from baseline in body weight, serum metabolic markers, and body composition were evaluated. Results A total of 17 patients completed the 8-week administration of tofogliflodin. No serious adverse events were noted. Hemoglobin A1c (HbA1c) decreased significantly, from 7.8% to 7.3% with 8-week ad- ministration of tofogliflozin. Both the body weight and body mass index (BMI) also decreased. In addition, a decreased renal function of the boundary zone and hemoconcentration were detected. As for body composi- tion, the free fat mass, total body water, extracellular water and intracellular water were all decreased signifi- cantly. Interestingly, the amount of fat mass did not change. The degree of improvement in HbA1c was corre- lated with the baseline fat mass and BMI. Conclusion An eight-week administration of tofogliflozin improved glycemic control and reduced the body weight and free fat mass in type 2 diabetic patients without affecting the fat mass.
    [Show full text]
  • Downloaded From
    JPET Fast Forward. Published on February 5, 2013 as DOI: 10.1124/jpet.113.203125 JPET FastThis articleForward. has not Publishedbeen copyedited on and February formatted. The 6, final2013 version as DOI:10.1124/jpet.113.203125 may differ from this version. JPET #203125 In vitro–in vivo correlation of the inhibition potency of sodium-glucose cotransporter inhibitors in rat: a pharmacokinetic and pharmacodynamic modeling approach Koji Yamaguchi, Motohiro Kato, Masayuki Suzuki, Hitoshi Hagita, Maiko Takada, Miho Ayabe, Yoshinori Aso, Masaki Ishigai, and Sachiya Ikeda Downloaded from Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, jpet.aspetjournals.org Japan (K.Y., M.K., M.S., M.T., M.A., Y.A, M.I., S.I.) Chugai Research Institute for Medical Science, Inc., 1-135 Komakado, Gotemba, Shizuoka 412-8513, at ASPET Journals on September 26, 2021 Japan (H.H.) 1 Copyright 2013 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on February 5, 2013 as DOI: 10.1124/jpet.113.203125 This article has not been copyedited and formatted. The final version may differ from this version. JPET #203125 Running title (60 characters including space): IVIVC for inhibition potency of SGLT inhibitors Correspondence to: Koji Yamaguchi Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan Telephone: +81-550-87-6708 Downloaded from Fax: +81-550-87-5397 E-mail: [email protected] jpet.aspetjournals.org Numbers of the manuscript: at ASPET Journals on September 26, 2021 Text pages: 43 Figures: 6 Tables: 4 References: 36 Words in Abstract: 229 Words in Introduction: 593 Words in Discussion: 1653 2 JPET Fast Forward.
    [Show full text]
  • Descargar Revista Completa
    Volumen 06 - Número 01 - 2015 Diabetes Periodicidad trimestral práctica Actualización y habilidades en Atención Primaria Editorial 01 Investigación y diabetes mellitus tipo 2 Domingo Orozco Beltrán Página 2 Diabetes y depresión. 02 Cuestión de riesgo Iván González Tejón, Susana González Tejón Página 8 La neuropatía autonómica. 03 Diagnóstico y manejo Javier Lafita Tejedor Página 15 Sujeto obeso y factores 04 de riesgo: ¿metformina o modificación de estilos de vida? Escarlata Angullo Martínez Página 20 Recopilación de comentarios 05 de artículos del blog de la redGDPS: http://redgedaps.blogspot.com Mateu Seguí Díaz Página 25 Las nuevas insulinas. 06 Bioequivalentes José Antonio Gimeno Orna Página 32 Diabetes práctica Actualización y habilidades en Atención Primaria SUMARIO: Director: Pedro Muñoz Cacho EDITORIAL Secretario de redacción: Josep Franch Nadal Investigación y diabetes mellitus tipo 2 2 Comité editorial: Domingo Orozco Beltrán Sara Artola Menéndez Javier Díez Espino Francisco Javier García Soidán ARTÍCULO DE REVISIÓN Asesores: Patxi Ezcurra Loiola Diabetes y depresión. Cuestión de riesgo 8 José Luis Martín Manzano Manel Mata Cases Iván González Tejón, Susana González Tejón Javier Mediavilla Bravo Jorge Navarro Pérez Mateu Seguí Díaz Rosario Serrano Martín HABILIDADES PRÁCTICAS Web redGDPS: La neuropatía autonómica. Diagnóstico y manejo 15 www.redgdps.org Javier Lafita Tejedor CASO CLÍNICO Avda. dels Vents, 9-13, Esc. B, 2.º 1.ª Sujeto obeso y factores de riesgo: ¿metformina 08917 Badalona [email protected] o modificación de estilos de vida? 20 www.euromedice.net Escarlata Angullo Martínez Depósito legal: B-15336-2010 ISSN: 2013-7923 © Copyright 2015: De los autores. BIBLIOGRAFÍA © Copyright de la edición 2015: EUROMEDICE, Ediciones Médicas, S.L.
    [Show full text]
  • Drugs in Pipeline for Type-2 Diabetes R Mahajan, K Gupta
    The Internet Journal of Pharmacology ISPUB.COM Volume 8 Number 2 Drugs In Pipeline For Type-2 Diabetes R Mahajan, K Gupta Citation R Mahajan, K Gupta. Drugs In Pipeline For Type-2 Diabetes. The Internet Journal of Pharmacology. 2009 Volume 8 Number 2. Abstract Hyperglycemia, obesity, insulin resistance, dyslipidemia and hypertension are interrelated cardiometabolic risk factors for the development of type-2 diabetes and metabolic syndrome. Prevalence of type-2 diabetes is growing at an alarming rate. Treatment target for type-2 diabetes is to keep daily glucose profile as close as possible to that of a non-diabetic person. Sulfonylureas, thiazolidinediones, meglitinides, biguanides and acarbose inhibitors are already being used in controlling glucose levels in type-2 diabetes. This review discusses the new drugs with novel mechanism of actions; which are in pipeline and were marketed recently or will be in market in near future. INTRODUCTION glimepiride); biguanides (phenformin, metformin); Type-2 diabetes is the most common metabolic disorder thiazolidinediones ( pioglitazone, rosiglitazone) meglitinides worldwide, and its prevalence is growing at an alarming rate (repaglinide, nateglinide); alpha-glucosidase inhibitors in both developed and developing countries. This growth has (acarbose, miglitol, voglibose) and miscellaneous ones been related to the increased prevalence of obesity. A cluster (aspartame, chromium picolinate, guargum, glucomannan), [4] of interrelated cardiometabolic risk factors is closely related available either singly or as combinations. With all these to the development of type-2 diabetes and cardiovascular available options, still, sometimes glucose control is not disease. Obesity, hyperglycemia and insulin resistance, maintained; and many patients ultimately have to put on dyslipidemia, inflammation, and hypertension represent insulin therapy.
    [Show full text]