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. 2023 Aug 1;6(8):e2330885.
doi: 10.1001/jamanetworkopen.2023.30885.

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

Jie Wei  1   2   3   4   5 , Hyon K Choi  6   7 , Nicola Dalbeth  8 , Xiaoxiao Li  4   5 , Changjun Li  5   9   10 , Chao Zeng  2   4   5   10 , Guanghua Lei  2   4   5   10 , Yuqing Zhang  6   7
Affiliations

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

Jie Wei et al. JAMA Netw Open. .

Abstract

Importance: Recurrent 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.

Objective: To 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 participants: This 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.

Exposures: Initiation of treatment with SGLT2i or active comparators.

Main outcomes and measures: The 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.

Results: Of 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 relevance: The 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wei reported receiving grant funding from Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders and the Science and Technology Department of Hunan Province, the Natural Science Foundation of Hunan Province, during the conduct of the study. Dr Choi reported receiving grant funding from Horizon Therapeutics for unrelated investigator-initiated research, serving on the ANI Pharmaceuticals, Inc, advisory board, the LG Chem Ltd steering committee, and from the Shanton Pharma data and safety monitoring board outside the submitted work. Dr Dalbeth reported receiving personal fees from AstraZeneca, Novartis AG, Dyve Biosciences, Horizon Therapeutics, Selecta Biosciences, Arthrosi Therapeutics, JW Pharmaceutical Corporation, PK Med, LG Chem Ltd, JPI, PTC Therapeutics, Protalix Bio Therapeutics, Unlocked Labs, and Hikma Pharmaceuticals PLC and nonfinancial support from AbbVie Inc outside the submitted work. Dr Zeng reported receiving grant funding from China’s Ministry of Science and Technology National Key Research and Development Plan, the National Natural Resources Foundation, and Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders during the conduct of the study. Dr Lei reported receiving grant funding from National Key Research and Development Plan and the National Natural Science Foundation of China during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Risk of Recurrent Gout Flares in Each Month Over 12-Month Period After Initiation of Treatment With Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) or Active Comparators
Active comparators consist of glucagonlike peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors.
Figure 2.
Figure 2.. Cumulative Incidence of the First Recurrent Gout Flare After Initiation of Treatment With Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) or Active Comparators
Active comparators consist of glucagonlike peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors.
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