SGLT2 Inhibitors in T2D Tied to New Risk Reduction Benefit

Individuals with type 2 diabetes on sodium-glucose cotransporter-2 (SGLT2) inhibitors may see a reduced gout risk, according to a population-based cohort study.

Compared to patients on a newly initiated glucagon-like peptide-1 (GLP1) receptor agonist, those on a SGLT2 inhibitor had a 36% reduced risk for developing gout (HR 0.64, 95% CI 0.57-0.72), reported Michael Fralick, MD, PhD, of Sinai Health System in Toronto, and colleagues.

Appearing in Annals of Internal Medicine, this equated to 2.9 fewer cases of incident gout per 1,000 person-years (95% CI -3.6 to -2.1).

"Gout is the most common form of inflammatory arthritis and adults with diabetes are at particularly high risk," Fralick explained to MedPage Today. "Identifying medications that reduce this risk is important, especially since one commonly used medication for gout -- febuxostat [Uloric] -- was recently found to increase a person's risk of death."

He highlighted that prior studies have reported a link between canagliflozin (Invokana) and lower serum urate, including a post-hoc analysis of the CANVAS clinical program published last month, but unknown was whether this reduction in uric acid would be large enough to lower an individual's gout risk.

"We were surprised to see that SGLT2 inhibitors were associated with such a large reduction in the risk of gout," said Fralick, adding that the current findings provide a "proof-of-principle that this class of medications might reduce the risk of gout in adults with diabetes."

For their study, Fralick's group drew on insurance claims appearing in a national database from 2013 to 2017. Overall, the study included nearly 300,000 adults with type 2 diabetes -- 152,000 of whom were newly prescribed an SGLT2 inhibitor and 144,000 of whom were prescribed a GLP1 receptor agonist. Patients with type 1 diabetes, gout, cancer, and HIV/AIDS were excluded from the analysis, as were those on dialysis or an SGLT2 combination pill.

Using a propensity score-matched model, patients were matched 1:1 for baseline characteristics, including comorbidities, other medications, and healthcare utilization, such as seeing an endocrinologist. In a sensitivity analysis that examined 1 year of treatment exposure, those prescribed an SGLT2 inhibitor had a 27% lower risk for incident gout versus matched patients newly prescribed a GLP1 receptor agonist (adjusted HR 0.73, 95% CI 0.66-0.82).

Another sensitivity analysis found that patients on a newly prescribed SGLT2 inhibitor had a 34% reduced risk for gout versus those newly starting on a dipeptidyl peptidase 4 (DPP-4) inhibitor (HR 0.66, 95% CI 0.58-0.75).

In addition to their glucose lowering capability, SGLT2 inhibitors have proven beneficial in other ways. The label for the first-in-class agent canagliflozin -- initially approved back in 2013 -- was recently expanded to include cardiovascular and renal preventions. Other currently approved SGLT2 agents include dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro).

The researchers pointed out how much of the new research on SGLT2 inhibitors is now moving beyond diabetes, as several trials currently underway are looking at patients without diabetes. However, none of the current trials are assessing this class as a prevention or treatment option for gout.

"SGLT2 inhibitors are one of the most effective classes of medications for adults with diabetes. Our study suggests they may have the added benefit of reducing the risk of gout," Fralick underscored.

One limitation to this study included a lack of data on relevant gout risk factors, including information on diet and body mass index.

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