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The clinical benefits of sodium–glucose cotransporter type 2 inhibitors in people with gout

Nature Reviews Rheumatology volume 20, pages 216–231 (2024)Cite this article

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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 risk in patients with gout are likely to be required to reduce mortality. Sodium–glucose cotransporter type 2 (SGLT2) inhibitors are approved for multiple indications owing to their ability to lower the risk of all-cause and cardiovascular death, hospitalizations for heart failure and chronic kidney disease progression, making them an attractive treatment option for gout. 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.

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Fig. 1: Potential urate-lowering and anti-inflammatory effects of SGLT2 inhibitors.

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Acknowledgements

The authors would like to thank S. Tanikella for assistance in generating the figures included in this manuscript.

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Authors and Affiliations

  1. Rheumatology & Allergy Clinical Epidemiology Research Center (RACER), Mongan Institute, Massachusetts General Hospital, Boston, MA, USA

    Chio Yokose, Natalie McCormick & Hyon K. Choi

  2. Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA

    Chio Yokose, Natalie McCormick & Hyon K. Choi

  3. Harvard Medical School, Boston, MA, USA

    Chio Yokose, Natalie McCormick, Meghan E. Sise, James L. Januzzi, Deborah J. Wexler & Hyon K. Choi

  4. Arthritis Research Canada, Vancouver, British Columbia, Canada

    Natalie McCormick & Hyon K. Choi

  5. The University of Nottingham, Nottingham, UK

    Abhishek Abhishek

  6. Department of Medicine, University of Auckland, Auckland, New Zealand

    Nicola Dalbeth

  7. Department of Rheumatology, Lille Catholic University, Saint-Philibert Hospital, Lille, France

    Tristan Pascart

  8. Université Paris Cité, Inserm UMR 1132 Bioscar, centre Viggo Petersen, Hôpital Lariboisière, Paris, France

    Frédéric Lioté

  9. Rheumatology Department, Saint-Joseph Paris Hospital, Paris, France

    Frédéric Lioté

  10. Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA

    Angelo Gaffo

  11. Birmingham VA Medical Center, Birmingham, AL, USA

    Angelo Gaffo

  12. Department of Medicine/Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    John FitzGerald

  13. Veterans Health Affairs, Greater Los Angeles, Los Angeles, CA, USA

    John FitzGerald

  14. Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, San Diego, CA, USA

    Robert Terkeltaub

  15. Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA

    Meghan E. Sise

  16. Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA

    James L. Januzzi

  17. Baim Institute for Clinical Research, Boston, MA, USA

    James L. Januzzi

  18. MGH Diabetes Center, Massachusetts General Hospital, Boston, MA, USA

    Deborah J. Wexler

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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.

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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.

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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

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