Can SGLT2 inhibitors prevent incident gout? A systematic review and meta-analysis

Purpose To collate the effect of SGLT2 inhibitors (SGLT2i) on adverse gout events in people with type 2 diabetes mellitus (T2DM). Methods PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched using appropriate keywords/MeSH/Emtree terms till January 25, 2022, to identify observational studies, randomized controlled trials (RCTs) or post hoc analysis reporting incident gout events and/or commencement of anti-gout drug in people with T2DM receiving SGLT2i versus those not receiving SGLT2i. Subgroup analyses were performed using comparators as placebo/other antidiabetic drugs and presence/absence of baseline hyperuricemia (uric acid >= 7 or < 7 mg/dl). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results We identified 5 studies (3 observational, 2 post hoc analysis of RCTs) pooling data retrieved from 568,010 people with T2DM. Pooled analysis showed that SGLT2i use was associated with 30% reduction in incident gout events/gout flares (HR 0.70, 95% CI: 0.59, 0.84, p < 0.001, I-2 = 84%). Sensitivity analysis after excluding the retrospective observational study showed similar estimates (HR 0.65, 95% CI: 0.60, 0.70, p < 0.001, I-2 = 0%). Subgroup analysis of data retrieved only from RCTs also showed significant benefits (HR 0.74, 95% CI: 0.55, 0.98, p = 0.03, I-2 = 0%). Pooled analysis of data from 2 studies showed that SGLT2i use led to a significant reduction in the need for commencement of new anti-gout drug (pooled HR 0.58, 95% CI: 0.48, 0.71, p < 0.001, I-2 = 0%). Consistent benefits were also observed for subgroup without baseline hyperuricemia (pooled HR 0.65, 95% CI: 0.47, 0.89, p < 0.01, I-2 = 0%). Conclusions SGLT2i may potentially prevent gout-related adverse events in people with T2DM.