Sodium glucose cotransporter 2 inhibitors and gout risk: a sequence symmetry analysis

To examine the association between sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and gout incidence in patients with diabetes is the objective.

National administrative data from the United States Veterans Health Administration were used to identify patients initiated on SGLT2-I from 2012 to 2020. Sequence symmetry analysis was performed to contrast the number of patients with incident gout within the year following SGLT2-I initiation to the number within the year preceding initiation. Exposure counterfactual analyses examined the relationship between potential therapeutic alternatives to SGLT2-I and risk for gout.

The primary outcome of incident gout was observed in 441 patients preceding SGLT2-I initiation and 273 patients following SGTL2-I (symmetry ratio (SR) = 0.62; 95% CI: 0.53-0.72). This finding remained consistent across multiple sensitivity analyses. A reduction in gout incidence was also observed in exposure counterfactual cohorts initiating dipeptidyl peptidase-4 inhibitor (SR = 0.67; 95% CI: 0.63-0.72) and thiazolidinediones (SR = 0.72; 95% CI: 0.65-0.79), but not glucagon-like peptide-1 receptor agonist (GLP1-RA) (SR = 0.93; 95% CI: 0.77-1.12).

The risk for incident gout was significantly reduced following SGLT2-I initiation. GLP1-RA had minimal to no impact on gout risk. Our findings support pleiotropic benefits of SGLT2-I use in patients with diabetes at elevated risk for gout. Key points • Early studies suggest SGLT2-inhibitors may decrease risk for gout • Our sequence symmetry analysis confirmed this observation • DPP4s and thiazolidinediones were also associated with lower gout risk • SLGT2 inhibitors may be beneficial in patients with diabetes at risk for gout.