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REVIEW Empagliflozin: a New Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

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REVIEW Empagliflozin: a New Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes FULL TEXT ARTICLE ISSN 1740-4398 A continuous publication, open access, peer-reviewed journal www.drugsincontext.com REVIEW Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes Joshua J Neumiller Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, WA, USA Citation Provenance Neumiller JJ. Empagliflozin: a new sodium-glucose co- Submitted, externally peer reviewed transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Drugs in Context 2014; 3: 212262. doi: 10.7573/ Dates dic.212262 Submitted: 4 March 2014 Accepted, subject to peer review: 5 March 2014 Copyright Revised manuscript submitted: 28 May 2014 © 2014 Neumiller JJ. This is an open-access article distributed Published: 11 June 2014 under the terms of the Creative Commons Attribution License Deed CC BY NC ND 3.0 which allows anyone to copy, Publisher & contact information distribute, and transmit the article provided it is properly Drugs in Context is published by Just Medical Media Ltd, 11 attributed in the manner specified below. No other uses Redgrove Park, Cheltenham, Gloucestershire GL51 6QY, UK; without permission. ISSN 1740-4398; Just Medical Media Limited is registered in England Number 6891187; VAT GB 945 1713 22 Correct attribution Copyright © 2014 Neumiller JJ. Published by Drugs in Context Julia Savory under Creative Commons Attribution License Deed CC BY NC Head of Digital Publishing and Submissions Management ND 3.0. http://dx.doi.org/10.7573/dic.212262 [email protected]; Tel: +44 (0)1242 910 999 Article URL Abbreviations http://www.drugsincontext.com/empagliflozin-a-new- AE, adverse event; bid, twice daily; CI, confidence interval; sodium-glucose-co-transporter-2-sglt2-inhibitor-for-the- CKD, chronic kidney disease; CV, cardiovascular; DPP-4, treatment-of-type-2-diabetes/ dipeptidyl-peptidase-4; eGFR, estimated glomerular filtration rate; EMA, European Medicines Agency; FDA, Food and Correspondence Drug Administration; FDC, fixed-dose combination; FPG, Joshua J Neumiller. Assistant Professor, Department of fasting plasma glucose; GLP-1, glucagon-like peptide 1; GLUT, Pharmacotherapy, College of Pharmacy, Washington State glucose transporter; HbA1c, glycosylated hemoglobin; MI, University, PO Box 1495, Spokane, WA 99218, USA. myocardial infarction; OAD, oral antidiabetes drug; OGTT, oral [email protected] glucose tolerance test; PPG, post-prandial glucose; qd, once daily; SBP, systolic blood pressure; SD, standard deviation; SE, standard error; SGLT1/2, sodium-glucose co-transporters; UGE, urinary glucose excretion; ZDF, Zucker diabetic fatty (rat). Drugs in Context • www.drugsincontext.com Drugs in Context 2014; 3: 212262 1 ISSN: 1740-4398 ENDOCRINOLOGY ediToriAL BOArd Specialist Editor-in-Chief Group Editor-in-Chief Professor Eva M Vivian, PharmD Christopher Blanchette, PhD, MBA Associate Professor, University of Wisconsin-Madison School of Associate Dean for Research and Research Associate Professor Pharmacy, Madison, WI, USA in the Department of Public Health Sciences at the University of North Carolina and Director of Health Economics & Outcomes Specialist Health Economics Editor Research at Otsuka America Pharmaceutical Inc, USA Dr Won Chan Lee, PhD Principal, Health Economics and Outcomes Research, IMS Expert Advisers – Epidemiology and biostatistics Consulting Group, Alexandria, VA, USA Alex K Exuzides, PhD Director, ICON Clinical Research Inc, California, USA Specialist Advisor – Epidemiology Professor Scott L Friedman, MD Professor Jennifer Robinson, MD Fishberg Professor of Medicine, Dean for Therapeutic Discovery Clinical Assistant Professor, Department of Pharmacotherapy, Chief, Division of Liver Diseases, Mount Sinai School of Washington State University College of Pharmacy, Spokane, Medicine, New York, USA WA, USA Carl De Moor, PhD Specialist editorial board members Senior Principal, Epidemiology and Leader Epidemiology, Safety and Risk Management Center of Excellence Americas, Marlon E Cerf, MD IMS Health Inc, USA Specialist Scientist, Diabetes Discovery Platform, South African Medical Research Council, South Africa Dr John H Walker, OCT, MBA, PhD Professor, Goodman School of Business, Brock University, Pamela Daniels, MBA, MPH, PhD St Catharines, Ontario, Canada Epidemiologist, Morehouse School of Medicine, 720 Westview Drive, SW, MRC Annex S-10, Atlanta, GA, USA Expert Adviser – Publication Ethics Professor Stuart T Haines, PharmD Dr Elizabeth (Liz) Wager Professor and Vice Chair for Clinical Services, Department of Publications Consultant, Princes Risborough, UK; Visiting Pharmacy Practice and Science, University of Maryland School Professor, University of Split School of Medicine, Croatia; Former of Pharmacy, Baltimore, MD, USA; Clinical Pharmacy Specialist, Chair (2009-2012), Committee on Publication Ethics (COPE) West Palm Beach VA Medical Center, West Palm Beach, FL, USA Sivaramakrishna Koganti, PhD Editor-in-Chief Emeritus Department of Internal Medicine, Carver College of Medicine, Dr George Kassianos, FRCGP, FESC, FBGTHA, FAcadMEd, University of Iowa, USA FFTM RCPSGlasg General Practitioner, Bracknell, Berkshire, UK; President British Professor Elaena Quattrocchi, PharmD Global & Travel Health Association Fellow of the European Associate Professor, Division of Pharmacy Practice, Arnold and Society of Cardiology Marie Schwartz College of Pharmacy and Health Sciences, Staten Island University Hospital, NY, USA Specialist Advisor – Clinical Pharmacology Evan Sisson, PharmD, MHA, CDE Dr Richard White, MA, PhD Virginia Commonwealth University, School of Pharmacy, Consulting Partner and Director, Oxford PharmaGenesis Ltd, UK Virginia, USA Junhua Yu Assistant Professor, Social, Behavioral and Administrative Sciences,Touro University College of Pharmacy, Vallejo, CA, USA To see the full Drugs in Context Editorial Board, please visit www.drugsincontext.com/editorial-board Drugs in Context • www.drugsincontext.com Drugs in Context 2014; 3: 212262 2 ISSN: 1740-4398 FULL TEXT ARTICLE A continuous publication, open access, peer-reviewed journal REVIEW Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes Joshua J Neumiller Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, WA, USA Citation on pharmacokinetics. In Phase II trials in patients with type 2 Neumiller JJ. Empagliflozin: a new sodium-glucose co- diabetes, empagliflozin provided improvements in glycosylated transporter 2 (SGLT2) inhibitor for the treatment of type 2 hemoglobin (HbA1c) and other measures of glycemic control diabetes. Drugs in Context 2014; 3: 212262. when given as monotherapy or add-on to metformin, as well as doi: 10.7573/dic.212262 reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but Abstract also reduced insulin doses. Across studies, empagliflozin was Type 2 diabetes is increasing in prevalence worldwide, and generally well tolerated with a similar rate of hypoglycemia to hyperglycemia is often poorly controlled despite a number placebo; however, patients had a slightly increased frequency of therapeutic options. Unlike previously available agents, of genital infections, but not urinary tract infections, versus sodium-glucose co-transporter 2 (SGLT2) inhibitors offer an placebo. Phase III studies have also reported a good safety insulin-independent mechanism for improving blood glucose profile along with significant improvements in HbA1c, weight levels, since they promote urinary glucose excretion (UGE) by and blood pressure, with no increased risk of hypoglycemia inhibiting glucose reabsorption in the kidney. In addition to versus placebo. Based on available data, it appears that glucose control, SGLT2 inhibitors are associated with weight loss empagliflozin may be a useful option in a range of patients; and blood pressure reductions, and do not increase the risk of however, clinical decisions will be better informed by the results hypoglycemia. of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™). Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with Keywords: Blood glucose, combination drug therapy, up to 90 g of glucose excreted per day. It can be administered empagliflozin, hemoglobin A1c protein, hypertension, obesity, orally, and studies of people with renal or hepatic impairment sodium-glucose co-transporter 2 (SGLT2) inhibitors, type 2 indicated empagliflozin needed no dose adjustment based diabetes Introduction [2–4]. Effective glycemic control is therefore considered central to patient management, and a number of glucose-lowering In patients with type 2 diabetes, higher levels of hyperglycemia therapies are available. Yet in clinical practice many patients do are associated with increasing risk of vascular events, with each not achieve glycemic goals [5]. The most frequently cited reason 1% increase in glycosylated hemoglobin (HbA1c) associated is the side-effect profiles of available agents, in particular with as much as 38% increased risk of mortality [1]. In patients hypoglycemia and weight gain, although unwillingness to with type 1 diabetes, intensive diabetes therapy has been begin insulin injections may also play a role [6,7]. Furthermore, clearly shown to reduce the incidence of clinical cardiovascular many patients do not maintain individualized glycemic goals,
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