Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes

Abstract

ImportanceRecurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown.ObjectiveTo examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes.Design, Setting, and ParticipantsThis population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners.ExposuresInitiation of treatment with SGLT2i or active comparators.Main Outcomes and MeasuresThe primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting.ResultsOf a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was −8.8 (95% CI, −17.2 to −0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of −6.1 (95% CI, −10.6 to −1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97).Conclusions and RelevanceThe findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.

SGLT2 Inhibitors and Uric Acid Homeostasis

“…The study utilized a baseline population characterized as having T2D and gout and then given either SGLT2is or comparators (e.g., GPL inhibitor). The study found that the gout patients given the SGLT2is had significantly fewer gout flares and significantly lower all causal mortality [7]. Both studies critically corroborated the link between tubular glucose and increased uric acid excretion by the kidney The potential benefits of SGLT2i for patients with gout has been recently reviewed [84].…”

“…These include improved cardiovascular and renal functions, an improved lipid profile, weight loss, and uric acid (primarily urate at physiological pH)-lowering effects [4][5][6]. The unexpected increase in urate excretion resulting from SGLT2i use suggests a significant potential benefit to those with hyperuricemia and urate pathologies [7] and highlights the need to better understand the well-known but unresolved relationship between urate levels and metabolic disorders, mainly in T2D.…”

Gout and its management

“…In this regard prescribers need to consider whether the medications used to manage these comorbidities influence the treatment of gout and vice versa. For example, there is emerging evidence that low‐dose colchicine may be beneficial in reducing cardiovascular events and that sodium‐glucose cotransporter 2 inhibitors lower the risk of recurrent gout flares and mortality in people with gout and type 2 diabetes 24 …”

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

“…Post hoc analyses of CVOT data and real-world studies have revealed that the use of SGLT2i therapy is associated with lower serum urate levels and reduced incidence of gout [ 115 – 119 ]. In addition, a recent cohort study indicated that people T2DM and gout were at lower risk of recurrent gout flares and mortality if they were treated with an SGLT2i, compared with other oral glucose-lowering therapies [ 120 ].…”