Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may reduce the risk for recurrent gout flares and early mortality compared with other diabetes treatments in patients with gout and type 2 diabetes, investigators report.

In an observational study of 5931 patients (mean age, 66 years), initiation of SGLT2i was significantly associated with a 19% lower risk for a first recurrent gout flare and a 21% lower risk for recurrent gout flares overall compared with initiation of glucagonlike peptide-1 receptor agonists (GLP-1 RA) or dipeptidyl peptidase-4 inhibitors (DPP-4i). Compared with GLP-1 RA alone, SGLT2 inhibitors were significantly associated with a 35% lower risk for recurrent flares, Guanghua Lei, MD, PhD, and Chao Zeng, MD, PhD, of Xiangya Hospital, Central South University in Changsha, Hunan, China, and colleagues reported in JAMA Network Open. Use of SGLT2i vs active comparators was associated with 8.1 and 8.8 fewer first and overall recurrent flares, respectively, per 1000 person-years.

SGLT2 inhibitor initiation also was significantly associated with a 29% lower risk for all-cause mortality compared with initiation of GLP-1 RA and DPP-4i, the investigators reported. The SGLT2i group had 6.1 fewer deaths per 1000 person-years than the active comparator group. In subgroup analysis, the lower risk for all-cause mortality among initiators of SGLT21 remained significant only compared with DPP-4i, not GLP-1 RA.

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Of the cohort, 11.2% had chronic kidney disease and 7.9% had heart failure. Myocardial infarction and stroke previously occurred in 9.1% and 3.7%, respectively.

In terms of mechanisms, the investigators suggested SGLT2i might increase kidney urate elimination. It may enhance the sirtuin-1 enzyme that inhibits xanthine oxidase,  suppress pyrin domain-containing 3 inflammasome activation, and curb interleukin 1β secretion. SGLT2i use might also improve kidney function and heart failure and reduce the use of loop or thiazides diuretics, and thus indirectly lower the risk for recurrent gout flares.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wei J, Choi HK, Dalbeth N, et al. Gout flares and mortality after sodium-glucose cotransporter-2 inhibitor treatment for gout and type 2 diabetes. JAMA Netw Open. Published online August 25, 2023. doi:10.1001/jamanetworkopen.2023.30885