Sodium–Glucose Cotransporter-2 Inhibitors and Severe Urinary Tract Infections: Reassuring Real-World Evidence
Authors: Kristian B. Filion, Oriana H. Yu
Journal: Annals of Internal Medicine (2019)

Editorials20 August 2019Sodium–Glucose Cotransporter-2 Inhibitors and Severe Urinary Tract Infections: Reassuring Real-World EvidenceKristian B. Filion, PhD and Oriana H. Yu, MD, MScKristian B. Filion, PhDMcGill University and Lady Davis Institute at the Jewish General Hospital, Montreal, Quebec, Canada (K.B.F., O.H.Y.)Search for more papers by this author and Oriana H. Yu, MD, MScMcGill University and Lady Davis Institute at the Jewish General Hospital, Montreal, Quebec, Canada (K.B.F., O.H.Y.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-1950 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Sodium–glucose cotransporter-2 (SGLT-2) inhibitors, the most recently approved class of antidiabetic drugs, reduce glycemia by inhibiting glucose reabsorption in the renal proximal tubule (1). Through this mechanism of action, these drugs also induce weight loss and confer cardiovascular benefits, including reductions in major adverse events and heart failure (2). As a result, SGLT-2 inhibitors were the first class of antidiabetic drugs to be approved for cardiovascular disease prevention and are now recommended as a preferred second-line therapy among patients with type 2 diabetes and known atherosclerotic cardiovascular disease who cannot attain glycemic control with metformin monotherapy (3).Because of the ...References1. Ghezzi C, Loo DDF, Wright EM. Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia. 2018;61:2087-97. [PMID: 30132032] doi:10.1007/s00125-018-4656-5 CrossrefMedlineGoogle Scholar2. Home P. Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia. 2019;62:357-69. [PMID: 30607467] doi:10.1007/s00125-018-4801-1 CrossrefMedlineGoogle Scholar3. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42:S90-102. [PMID: 30559235] doi:10.2337/dc19-S009 CrossrefMedlineGoogle Scholar4. Geerlings SE, Brouwer EC, Gaastra W, et al. Effect of glucose and pH on uropathogenic and non-uropathogenic Escherichia coli: studies with urine from diabetic and non-diabetic individuals. J Med Microbiol. 1999;48:535-9. [PMID: 10359302] CrossrefMedlineGoogle Scholar5. U.S. Food and Drug Administration. FDA drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. 4 December 2015. Accessed at https://wayback.archive-it.org/7993/20170112031533/http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm on 19 June 2019. Google Scholar6. Puckrin R, Saltiel MP, Reynier P, et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55:503-14. [PMID: 29484489] doi:10.1007/s00592-018-1116-0 CrossrefMedlineGoogle Scholar7. Dave CV, Schneeweiss S, Kim D, et al. Sodium–glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections. A population-based cohort study. Ann Intern Med. 2019;171:248-56. doi:10.7326/M18-3136 LinkGoogle Scholar8. Lund JL, Richardson DB, Stürmer T. The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application. Curr Epidemiol Rep. 2015;2:221-8. [PMID: 26954351] CrossrefMedlineGoogle Scholar9. Filion KB, Suissa S. DPP-4 inhibitors and heart failure: some reassurance, some uncertainty. Diabetes Care. 2016;39:735-7. [PMID: 27208376] doi:10.2337/dci15-0036 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: McGill University and Lady Davis Institute at the Jewish General Hospital, Montreal, Quebec, Canada (K.B.F., O.H.Y.)Acknowledgment: The authors thank Dr. Laurent Azoulay for his helpful suggestions on an earlier version of this editorial.Financial Support: Dr. Filion holds a Chercheur-Boursier Junior II award from the Fonds de Recherche du Québec – Santé (Quebec Foundation for Health Research) and a William Dawson Scholar award from McGill University. Dr. Yu holds a Chercheur-Boursier Clinicien Junior 1 award from the Fonds de Recherche du Québec – Santé.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1950.Corresponding Author: Kristian B. Filion, PhD, Associate Professor and William Dawson Scholar, Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Centre for Clinical Epidemiology, Lady Davis Institute - Jewish General Hospital, 3755 Cote Ste-Catherine Road, H-410.1, Montreal, Quebec H3T 1E2, Canada; e-mail, kristian.[email protected]ca.Current Author Addresses: Dr. Filion: Lady Davis Institute - Jewish General Hospital, 3755 Cote Ste-Catherine Road, H-410.1, Montreal, Quebec H3T 1E2, Canada.Dr. Yu: Lady Davis Institute - Jewish General Hospital, 3755 Cote Ste-Catherine Road, E-104, Montreal, Quebec H3T 1E2, Canada.This article was published at Annals.org on 30 July 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSodium–Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections Chintan V. Dave , Sebastian Schneeweiss , Dae Kim , Michael Fralick , Angela Tong , and Elisabetta Patorno Metrics Cited byClinical spectrum, etiology and outcome of infectious disease emergencies in adult diabetic patients in northern IndiaThe present and future scope of real‐world evidence research in diabetes: What questions can and cannot be answered and what might be possible in the future?No increased risk of UTIs with SGLT-2 inhibitor use 20 August 2019Volume 171, Issue 4Page: 289-290KeywordsFood and Drug AdministrationGenitourinary infectionsHazard ratioHypoglycemicsPyelonephritisRelative riskSafetySafety studiesType 2 diabetes ePublished: 30 July 2019 Issue Published: 20 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...