ABSTRACT Gout is the most common form of inflammatory arthritis worldwide and is characterized by painful recurrent flares of inflammatory arthritis that are associated with a transiently

increased risk of adverse cardiovascular events. Furthermore, gout is associated with multiple cardiometabolic–renal comorbidities such as type 2 diabetes, chronic kidney disease and

cardiovascular disease. These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of serum urate

concentrations and traditional cardiovascular risk factors. Although better implementation of standard gout care could improve gout outcomes, deliberate efforts to address the cardiovascular

These medications have also been shown to lower serum urate concentrations, the causal culprit in gout risk, and are associated with a reduced risk of incident and recurrent gout,

potentially owing to their purported anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both the symptoms of gout and its comorbidities. KEY POINTS *

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have revolutionized the management of type 2 diabetes, heart failure and chronic kidney disease and have been incorporated into

multiple subspecialty management guidelines. * SGLT2 inhibitors hold promise as an attractive multi-purpose treatment option for patients with gout to simultaneously address

cardiometabolic–renal comorbidities and gout-related morbidity. * SGLT2 inhibitors have been shown to lower serum urate concentrations and the risk of incident and recurrent gout flares

without apparently increasing the risk of paradoxical gout flares. * The exact mechanisms underlying the urate-lowering and anti-gout effects of SGLT2 inhibitors remain under active

investigation but might involve enhanced uricosuria and anti-inflammatory pathways. * Although additional research is required to determine the role of SGLT2 inhibitors in gout management,

available evidence suggests that these drugs have the potential to improve outcomes among patients with gout. Access through your institution Buy or subscribe This is a preview of

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS EXCESS COMORBIDITIES IN GOUT: THE CAUSAL PARADIGM AND

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ACKNOWLEDGEMENTS The authors would like to thank S. Tanikella for assistance in generating the figures included in this manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Rheumatology

& Allergy Clinical Epidemiology Research Center (RACER), Mongan Institute, Massachusetts General Hospital, Boston, MA, USA Chio Yokose, Natalie McCormick & Hyon K. Choi * Division

of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA Chio Yokose, Natalie McCormick & Hyon K. Choi * Harvard Medical School, Boston, MA, USA Chio

Yokose, Natalie McCormick, Meghan E. Sise, James L. Januzzi, Deborah J. Wexler & Hyon K. Choi * Arthritis Research Canada, Vancouver, British Columbia, Canada Natalie McCormick & 

Hyon K. Choi * The University of Nottingham, Nottingham, UK Abhishek Abhishek * Department of Medicine, University of Auckland, Auckland, New Zealand Nicola Dalbeth * Department of

Rheumatology, Lille Catholic University, Saint-Philibert Hospital, Lille, France Tristan Pascart * Université Paris Cité, Inserm UMR 1132 Bioscar, centre Viggo Petersen, Hôpital

Lariboisière, Paris, France Frédéric Lioté * Rheumatology Department, Saint-Joseph Paris Hospital, Paris, France Frédéric Lioté * Division of Clinical Immunology and Rheumatology, University

of Alabama at Birmingham, Birmingham, AL, USA Angelo Gaffo * Birmingham VA Medical Center, Birmingham, AL, USA Angelo Gaffo * Department of Medicine/Rheumatology, David Geffen School of

Medicine at UCLA, Los Angeles, CA, USA John FitzGerald * Veterans Health Affairs, Greater Los Angeles, Los Angeles, CA, USA John FitzGerald * Division of Rheumatology, Allergy and

Immunology, Department of Medicine, University of California San Diego, San Diego, CA, USA Robert Terkeltaub * Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA Meghan

E. Sise * Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA James L. Januzzi * Baim Institute for Clinical Research, Boston, MA, USA James L. Januzzi * MGH Diabetes

Center, Massachusetts General Hospital, Boston, MA, USA Deborah J. Wexler Authors * Chio Yokose View author publications You can also search for this author inPubMed Google Scholar * Natalie

McCormick View author publications You can also search for this author inPubMed Google Scholar * Abhishek Abhishek View author publications You can also search for this author inPubMed 

Google Scholar * Nicola Dalbeth View author publications You can also search for this author inPubMed Google Scholar * Tristan Pascart View author publications You can also search for this

author inPubMed Google Scholar * Frédéric Lioté View author publications You can also search for this author inPubMed Google Scholar * Angelo Gaffo View author publications You can also

search for this author inPubMed Google Scholar * John FitzGerald View author publications You can also search for this author inPubMed Google Scholar * Robert Terkeltaub View author

publications You can also search for this author inPubMed Google Scholar * Meghan E. Sise View author publications You can also search for this author inPubMed Google Scholar * James L.

Januzzi View author publications You can also search for this author inPubMed Google Scholar * Deborah J. Wexler View author publications You can also search for this author inPubMed Google

Scholar * Hyon K. Choi View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS C.Y. and N.M. researched data for the article. C.Y. wrote the

article. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Chio Yokose.

ETHICS DECLARATIONS COMPETING INTERESTS N.D. has received consulting fees, speaker fees or grants from Arthrosi, AstraZeneca, Dyve Biosciences, Hikma, Horizon, JPI, JW Pharmaceutical

Corporation, LG Chem, Novartis, PK Med, Protalix, PTC Therapeutics, Selecta and Unlocked Labs, outside the submitted work. F.L. has received consulting fees from Horizon Biosciences, Mayoly

Spindler, Novartis, Olatec and SOBI-Selecta, and unrestricted grants for the European Crystal Network workshops from Arthrosi, AstraZeneca, Dyve Biosciences, Horizon Biosciences, Mayoly

Spindler and Olatec, outside the submitted work. A.G has served as consultant SOBI, PK Med and serves on a data monitoring committee for Atom Bioscience. J.L.J. is a Trustee of the American

College of Cardiology and a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, HeartFlow, Innolife and Novartis; has received

consulting income from Abbott Diagnostics, AstraZeneca, Beckman Coulter, Jana Care, Janssen, Novartis, Prevencio, Quidel and Roche Diagnostics; and participates in clinical end point

committees/data safety monitoring boards for AbbVie, Abbott, Bayer, Siemens, Pfizer and Takeda, outside the submitted work. R.T. has served or serves as a consultant for Acquist

Therapeutics, Allena, AstraZeneca, Atom Bioscience, Fortress/Urica, Generate Biomedicines, Horizon Therapeutics, LG Chem, Selecta Biosciences and Synlogic, and was a previous recipient of a

research grant from AstraZeneca. R.T. serves as the non-salaried President of the G-CAN (Gout, Hyperuricemia and Crystal-Associated Disease Network) research society; over its 9 years of

existence, G-CAN annually has received unrestricted arms-length grant support from pharma donors. D.J.W. serves on a data monitoring committee for Novo Nordisk, outside the submitted work.

H.K.C. reports research support from Ironwood and Horizon, and consulting fees from Horizon, Ironwood, Kowa, Selecta, Takeda and Vaxart. M.E.S. receives research funding from AbbVie, Angion,

Cabaletta, EMD-Serono, Gilead, Novartis, Otsuka and Roche; serves on scientific advisory boards for Calliditas, Mallinckrodt, Novartis, Travere and Vera; and serves as a DSMB member for

Alpine Immunosciences. T.P. has received consulting and speaker fees from Novartis and consulting and research grants from Horizon Pharmaceuticals. C.Y., J.F., N.M. and A.A. declare no

competing interests. PEER REVIEW PEER REVIEW INFORMATION _Nature Reviews Rheumatology_ thanks Mainak Banerjee and the other, anonymous, reviewer(s) for their contribution to the peer review

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and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yokose, C., McCormick, N., Abhishek, A. _et al._ The clinical benefits of sodium–glucose cotransporter type

2 inhibitors in people with gout. _Nat Rev Rheumatol_ 20, 216–231 (2024). https://doi.org/10.1038/s41584-024-01092-x Download citation * Accepted: 07 February 2024 * Published: 12 March 2024

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