SGLT2 Inhibitors Could Play a Role in Treating Gout

Chio Yokose, MD, MSc

Credit: Twitter

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors—a popular drug class in the management of cardiometabolic and diabetic conditions— may provide improved outcomes in the treatment of gout and its common comorbidities, according to a new review.¹

A multinational team of investigators recently published a review article suggesting that the mechanism of SGLT2 inhibition in patients with the arthritic disease could provide anti-inflammatory benefit, while additionally reducing risk of cardiovascular and renal outcomes in such patients—as the drug class is already indicated to treat.

The review team, led by Chio Yokose, MD, MSc, of the Rheumatology & Allergy Clinical Epidemiology Research Center (RACER) at Mongan Institute, Massachusetts General Hospital, described the characteristics of gout and its most common comorbidities. Gout is the most common type of inflammatory arthritis globally, they noted, generally presenting by “painful recurrent flares…that are associated with a transiently increased risk of cardiovascular events.”

The condition is additionally linked to increased risk of type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular disease, Yokose and colleagues explained.

“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,” the team wrote. “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.”

It's with this latter sentiment that the team suggested the potential of SGLT2 inhibitors as an “attractive treatment option for gout.” The drug class—in forms of options including empagliflozin (Jardiance); dapagliflozin (Farxiga); canagliflozin (Invokana); and ertugliflozin (Steglaro)—has reached an approximate dozen-plus indications through the US Food and Drug Administration (FDA) since 2016 to treat type 2 diabetes², cardiovascular event risk including heart failure³, and CKD.⁴

Yokose and colleagues pointed to a multifactorial benefit with SGLT2 inhibition in patients with gout—addressing both cardiometabolic-renal risks as well as morbidity associated with gout.¹ They noted the drug class has been shown to lower serum urate concentration, the primary driver of gout incidence and severity, as well as the risk of incident and recurrent gout flares “without apparently increasing the risk of paradoxical gout flares.” This latter benefit would suggest a correlation between the observed anti-inflammatory benefit observed in treated patients with cardiometabolic-renal disease, and a similar effect in rheumatic patients.

This is not the first analysis to consider a potential role in gout management for the SGLT2 inhibitor class. A study presented during the European Congress on Rheumatology (EULAR) 2023 meeting last May showed initiating an SGLT2 inhibitor significantly reduced the risk of incident gout among at-risk patients with type 2 diabetes, compared to other drug classes including DPP-4 inhibitors (hazard ratio [HR], 0.54; 95% CI, 0.39 – 0.74), GLP-1 receptor agonists (HR, 0.39; 95% CI, 0.24 – 0.64), and sulfonylurea (HR, 0.61; 95% CI, 0.46 – 0.80).⁵

All the same, these promising clinical data come with the disclosure that investigators are still seeking to understand the urate-lowering and anti-gout properties of SGLT2 inhibitors, Yokose and colleagues noted.¹ They suggested such mechanisms may be due to enhanced uricosuria and anti-inflammatory pathways in SGLT2 inhibition.

All the same, the dynamic drug class appears to have a promising role to play in gout.

“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,” the investigators concluded.

References

1. ^{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}
2. ^{Kunzmann K. FDA Approves Pfizer and Merck's Ertugliflozin for Type 2 Diabetes. HCPLive. Published December 20, 2017. https://www.hcplive.com/view/fda-approves-pfizer-and-mercks-ertugliflozin-for-type-2-diabetes}
3. ^{Campbell P. Dapagliflozin Approved for Reducing Risk of Hospitalization for Heart Failure. HCPLive. Published October 21, 2019. https://www.hcplive.com/view/fda-expands-dapagliflozin-label-to-include-reducing-risk-of-cv-death-in-heart-failure}
4. ^{Campbell P. Empagliflozin (Jardiance) Receives CKD Approval from US FDA. HCPLive. Published September 22, 2023. https://www.hcplive.com/view/empagliflozin-jardiance-receives-ckd-approval-from-us-fda}
5. ^{Campbell P. For People with Diabetes, Starting an SGLT2 Inhibitor Could Lower Gout Risk. HCPLive. Published June 2, 2023. https://www.hcplive.com/view/for-people-with-diabetes-sglt2-inhibitor-could-lower-gout-risk}