Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan

Chung, Mu‐Chi; Hung, Peir-Haur; Hsiao, Po‐Jen; Wu, Laing-You; Chang, Chao‐Hsiang; Wu, Ming‐Ju; Shieh, Jeng-Jer; Chung, Chi-Jung

doi:10.1001/jamanetworkopen.2021.35353

Cited by 28 publications

(16 citation statements)

References 38 publications

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“…Previous post hoc analyses of randomized clinical trials [23][24][25]27 showed that SGLT2i reduced serum urate level, incident hyperuricemia, and incident gout in patients with type 2 diabetes or chronic heart failure, compared with placebo. Several observational studies 22,26,28,29 also reported that initiation of SGLT2i treatment was associated with a lower risk of incident gout than initiation of DPP-4i or GLP-1 RA treatment in patients with type 2 diabetes. However, to our knowledge, no study has previously assessed whether SGLT2i reduces the risk of recurrent gout flares.…”

Section: Discussionmentioning

confidence: 99%

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

Wei,

Choi,

Dalbeth

et al. 2023

JAMA Netw Open

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wei,

Choi,

Dalbeth

et al. 2023

JAMA Netw Open

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“…In fact, in two population‐based new‐user cohort studies, SGLT2 inhibitor use was associated with significantly reduced risk of gout when compared to individuals with T2DM who were prescribed GLP‐1RAs 38,39 . Several studies have also observed significant anti‐gout benefits with SGLT2 inhibitors versus dipeptidyl peptidase (DPP)‐4 inhibitors in T2DM 39–41 . One unique feature seen with SGLT2 inhibitor therapy is an up to twofold increase in fasting ketone, that is, BHB levels, which have significant anti‐inflammatory effects via NLRP‐3 inflammasome inhibition, and antioxidant effects via SIRT1 activation 42 .…”

Section: Discussionmentioning

confidence: 99%

“…38,39 Several studies have also observed significant anti-gout benefits with SGLT2 inhibitors versus dipeptidyl peptidase (DPP)-4 inhibitors in T2DM. [39][40][41] One unique feature seen with SGLT2 inhibitor therapy is an up to twofold increase in fasting ketone, that is, BHB levels, which have significant anti-inflammatory effects via NLRP-3 inflammasome inhibition, and antioxidant effects via SIRT1 activation. 42 Given the inverse relationship between SIRT1 and xanthine oxidase activity, SGLT2 inhibitors may also decrease xanthine oxidase activity by this SIRT1-mediated effect, thereby lowering the local generation of ROS and intracellular uric acid.…”

Section: Discussionmentioning

confidence: 99%

Serum uric acid lowering and effects of sodium‐glucose cotransporter‐2 inhibitors on gout: A meta‐analysis and meta‐regression of randomized controlled trials

Banerjee

Pal

Maisnam

et al. 2023

Diabetes Obesity Metabolism

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Aims To pool the effects of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF). Methods PubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1‐year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti‐gout drugs (SUA‐lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse‐variance method with a random‐effects model. Mixed‐effects model univariate meta‐regression analysis was performed. Results Five RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout‐related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45‐0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P‐interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57‐0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between‐trial heterogeneity (HR 0.46, 95% CI 0.39‐0.55; I2 = 0%). Univariate meta‐regression found no impact of baseline SUA, SUA lowering on follow‐up, diuretic use, or other variables on their anti‐gout effects. Conclusion We found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA‐lowering effects suggests that metabolic and anti‐inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti‐gout benefits.

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“…The use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95). A sensitivity analysis performed with gout-related medication also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97) 32 .…”

Section: Role Of Sglt2i In Hyperuricemia and Goutmentioning

confidence: 94%

Sodium glucose co-transport 2 inhibitors for gout treatment

Somagutta

Luvsannyam

Jain³

et al. 2022

Discoveries

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Hyperuricemia remains the most prevalent cause of gout. Gout patients present with joint inflammation and uric acid crystals deposition manifesting as tophi. The association of gout with increased risk of insulin resistance, diabetes, metabolic disorders, increased cardiometabolic risk, and kidney disease is well established. These factors influence the treatment plan, and current treatment options have limited cardiovascular risk reduction. So the need for novel treatments with a broad range of coverage for the complications is warranted. Sodium-glucose cotransporter 2 inhibitors are novel drugs approved for treating type-2 diabetes. They prevent glucose reabsorption and lower serum uric acid levels. Recently few studies have studied their association with reducing the risk of gout. They may help address the gout related complications through their recorded benefit with weight loss, improved insulin resistance, and cardiovascular benefits in recent studies. SGLT2-Is may be useful to reduce the risk of gout in individuals with type 2 diabetes. Limited literature is available on the safety and efficacy of these novel antidiabetic drugs in patients with gout. This review is aimed to summarize the current knowledge on the role and effectiveness of novel antidiabetic medication as an early therapeutic option in gout patients.

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Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan

Cited by 28 publications

References 38 publications

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

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

Serum uric acid lowering and effects of sodium‐glucose cotransporter‐2 inhibitors on gout: A meta‐analysis and meta‐regression of randomized controlled trials

Sodium glucose co-transport 2 inhibitors for gout treatment

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