Taichung City, Taiwan—Could the use of a common diabetes drug reduce the incidence of gout in T2DM patients? A nationwide cohort study conducted in Taiwan suggests that might be the case.

Researchers from China Medical University found a significant 11% risk reduction in the incidence of gout in 47,405 patients with T2DM who received an SGLT2 inhibitor. In the study, reported in JAMA Network Open, those patients were compared with 4,405 propensity score—matched individuals receiving DPP4 inhibitors.

While the effect appeared especially strong with dapagliflozin, researchers note that the benefits of SGLT2 inhibitor use in T2DM patients in lowering gout risk did not differ across subgroups.

"The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels," the study points out. "However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established."

The research team sought to determine whether prescribed SGLT2 inhibitors had any association with lower gout incidence in patients with T2DM.

The study involved analysis of the records of all patients with incident T2DM in Taiwan National Health Institution databases between May 1, 2016, and December 31, 2018. Data analysis was conducted from April 1 to June 30, 2021.

Researchers based a gout diagnosis on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM).

Of the 231,208 patients with T2DM included in the population, 49.22% were women, and the mean (SD) age was 61.53 years. The authors report that the overall gout incidence was 20.26 per 1,000 patient-years for SGLT2 inhibitor users and 24.30 per 1,000 patient-years for DPP4 inhibitor users.

"When potential risk factors were adjusted in the propensity score–matched population, use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95)," the authors explain. "A sensitivity analysis, performed when a gout diagnosis was ascertained using the ICD-9-CM or ICD-10-CM code with gout-related medication, also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97)."

The researchers conclude that their results support the hypothesis that T2DM patients who are receiving SGLT2 inhibitors may have a lower risk for gout compared with those receiving DPP4 inhibitors.

Background information in the articles advises that T2DM is associated with a risk of hyperuricemia due to insulin resistance or hyperinsulinemia, which decreases urinary urate secretion. "Hyperuricemia, in turn, is associated with a risk of diabetic kidney disease progression and cardiovascular disease," the authors note. "Gout development is a severe condition in which cardiovascular comorbidities are often frequent."

SGLT2 inhibitors, which reduce blood glucose levels, are currently the standard intervention for preventing diabetic kidney disease progression and cardiovascular disease in patients with T2DM.

The study points out that associations between baseline blood urate levels, cardiorenal outcomes, and death have also been observed in a large-scale SGLT2 inhibitor trial. In addition, reductions in blood urate levels have been shown to contribute to modest but significant SGLT2 inhibitor effects in lowering cardiovascular death.

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