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Effects of sodium-glucose cotransporter-2 inhibitors on serum urate levels and gout in patients with and without type 2 diabetes: a systematic review and network meta-analysis

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Abstract

Background

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors can decrease serum uric acid (sUA) levels and have potential in the management of glucose levels and cardiorenal protection in patients.

Aim

This systematic review and network meta-analysis aimed to investigate the effects of SGLT-2 inhibitors on sUA levels and incidence of gout in patients with or without type 2 diabetes.

Method

A systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and Clinical Trials databases was performed to retrieve relevant articles published from inception to April 27, 2025, focusing on the impact of SGLT-2 inhibitors on sUA levels or the incidence of gout in the study participants. We performed a Bayesian random-effects network meta-analysis of the included studies using the Markov Chain Monte Carlo simulation techniques. The grading of recommendations, assessment, development, and evaluation approach was used to assess the certainty of the evidence.

Results

A total of 57 trials were included. All SGLT-2 inhibitors reduced sUA levels. These inhibitors demonstrated a spectrum of sUA-lowering effects, with empagliflozin and dapagliflozin exhibiting particularly robust efficacy. Specifically, empagliflozin (10 mg: − 43 [95% CI − 52.45 to − 33.66]; 25 mg: − 41.99 [95% CI − 51.93 to − 31.9]; 50 mg: − 35.77 [95% CI − 68.04 to − 3.53]) and dapagliflozin (5 mg: − 36.91 [95% CI − 49.5 to − 24.46]; 10 mg: − 34.98 [95% CI − 43.75 to − 26.44]) displayed superior reductions in sUA levels compared to other agents within the class. Although there was a potential reduction in the incidence of gout associated with SGLT-2 inhibitors, the difference was not statistically significant.

Conclusion

Future long-term studies should consider SGLT-2 inhibitors for individuals requiring sUA reduction and gout management. These results could serve as a reference for future guidelines addressing the treatment of individuals with diabetes, necessitating sUA lowering and gout management.

Trial Registration PROSPERO registration number CRD42024521695.

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Acknowledgements

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Funding

Na Su was supported by grants from Sichuan Province Science and Technology Support Program (grant number 2023JDR0243) and Health Commission Program (grant number 2020-111). Qiaozhi Hu was supported by Sichuan Science and Technology Support Program (grant number: 2023NSFSC1696). This study was supported by the National Key Clinical Specialties Construction Program.

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Authors and Affiliations

  1. Department of Pharmacy, West China Hospital of Sichuan University, Chengdu, 610041, China

    Qiaozhi Hu & Na Su

  2. West China School of Medicine, Sichuan University, Chengdu, 610041, China

    Qiaozhi Hu

  3. Department of Pharmacy, Jiangxi Mental Health Center, Nanchang, 330029, China

    Shiwen Yang

  4. West China School of Pharmacy, Sichuan University, 37# Guoxue Road, Chengdu, 610041, Sichuan, China

    Bofei Zhang & Na Su

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Correspondence to Na Su.

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Hu, Q., Yang, S., Zhang, B. et al. Effects of sodium-glucose cotransporter-2 inhibitors on serum urate levels and gout in patients with and without type 2 diabetes: a systematic review and network meta-analysis. Int J Clin Pharm (2025). https://doi.org/10.1007/s11096-025-01950-y

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Keywords

  • Bayesian
  • Gout
  • Network meta-analysis
  • Serum uric acid
  • SGLT-2 inhibitors

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