SGLT2 Inhibitors and Gout

USA: Sodium-glucose cotransporter type 2 (SGLT2) inhibitors may provide improved outcomes in treating gout and its common comorbidities, a recent review has shown. SGLT2 inhibitors are a popular drug class in the management of cardiometabolic and diabetic conditions.

The review, published in Nature Reviews Rheumatology, suggested that the mechanism of SGLT2 inhibition in patients with arthritic disease could provide anti-inflammatory benefits while reducing the risk of renal and cardiovascular outcomes in such patients—as the drug class is already indicated to treat.

Characteristics of Gout and Comorbidities

Chio Yokose, Massachusetts General Hospital, Boston, MA, USA, and colleagues described the characteristics of gout and its most common comorbidities. They noted that gout is the most common form of inflammatory arthritis worldwide, which is characterized by painful recurrent flares of inflammatory arthritis and is associated with a transiently increased risk of adverse cardiovascular events.

Furthermore, gout is associated with various cardiometabolic–renal comorbidities such as:

• Chronic kidney disease (CKD)
• Type 2 diabetes
• Cardiovascular disease (CVD)

These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of traditional cardiovascular risk factors and serum urate concentrations.

The researchers add, "Although better implementation of standard gout care could improve gout outcomes, there is a need for deliberate efforts to address the CV risk in gout patients to reduce mortality."

SGLT2 Inhibitors as a Treatment Option

SGLT2 inhibitors are approved for multiple indications owing to their ability to lower the risk of hospitalizations for heart failure and CKD, all-cause, and cardiovascular death, making them an attractive treatment option for gout. These medications have been also shown to reduce serum urate concentrations, the causal culprit in gout risk, and are linked with a reduced risk of incident and recurrent gout, potentially due to their anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both gout symptoms and its comorbidities.

According to the authors, 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 in May 2023 showed initiating an SGLT2 inhibitor significantly lowered the risk of incident gout among at-risk patients with type 2 diabetes, compared to other drug classes, including:

• GLP-1 receptor agonists (HR, 0.39)
• DPP-4 inhibitors (hazard ratio [HR], 0.54)
• Sulfonylurea (HR, 0.61)

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

“Although additional research is needed to determine SGLT2 inhibitors' role in gout management, available evidence indicates that these drugs have the potential to improve outcomes among gout patients,” the researchers concluded.

Reference

Yokose, C., McCormick, N., Abhishek, A., Dalbeth, N., Pascart, T., Lioté, F., Gaffo, A., FitzGerald, J., Terkeltaub, R., Sise, M. E., Januzzi, J. L., Wexler, D. J., & Choi, H. K. (2024). The clinical benefits of sodium–glucose cotransporter type 2 inhibitors in people with gout. Nature Reviews Rheumatology, 20(4), 216-231. https://doi.org/10.1038/s41584-024-01092-x