SGLT2 inhibitors a promising gout medication in T2D

The use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors lowers the risk of incident gout or recurrent gout flares among patients with type 2 diabetes who are taking metformin, as shown in a study.

In a large cohort of adult T2D patients on metformin, SGLT2 inhibitor users had 2.64 fewer cases of incident gout per 1,000 person-years compared with sulfonylurea users (4.27 vs 6.91 events per 1,000 person-years). [JAMA Intern Med 2024;doi:10.1001/jamainternmed.2024.0376]

SGLT2 inhibitor use was associated with a 38-percent lower risk of incident gout (hazard ratio [HR], 0.62, 95 percent CI, 0.48–0.80), independent of sex, age, or baseline diuretic use.

The observed benefit with SGLT2 inhibitors extended to the subgroup of T2D patients with existing gout, with the rate of recurrent flares being 33-percent lower relative to sulfonylurea (rate ratio, 0.67, 95 percent CI, 0.55–0.82). This corresponded to 21 fewer flares per 1,000 person-years among SGLT2 inhibitor versus sulfonylurea users.

“SGLT2 inhibitor use was also associated with a 66-percent lower risk for incident gout cases resulting in an emergency department [ED] visit or hospitalization, as well as a 13-percent lower risk of major adverse cardiovascular events [MACE], with 4 fewer MACE events per 1,000 person-years,” the investigators noted.

Taken together, the findings suggest that SGLT2 inhibitors, consistent with their known urate-lowering effects, may reduce gout risk for T2D patients “who need a second-line agent after metformin and provide an attractive option to simultaneously address the high burden of gout and cardiometabolic sequelae in … diabetes,” they added.

This sequential, new-user comparative effectiveness study, which used target trial emulation framework, included 34,604 propensity score-matched adults (mean age 60 years, 60 percent male) with T2D receiving metformin monotherapy in a Canadian general population database; half initiated an SGLT2 inhibitor and the other half, a sulfonylurea.

By using a target trial emulation with an active comparator new-user design, the study aimed at reducing bias and getting cause-and-effect results for SGLT2 inhibitor use and gout risk. Such an approach facilitated similar starting points (baseline characteristics) for the groups being compared and defined when follow-up and treatment assignment began, as the investigators pointed out.

“We used an entire population-based database, which makes these findings likely generalizable, with data on dispensed medications (as opposed to issued prescriptions), reducing exposure misclassification. We also conducted several sensitivity analyses (including application of propensity score overlap weighting, involving all comparison medication initiators), with results closely consistent with our primary findings, supporting their robustness,” they said.

On the other hand, there were no available data on race and ethnicity, according to the researchers, who called for additional studies stratified by laboratory data and by race and ethnicity to explore potential heterogenous treatment effects of SGLT2 inhibitors.