Reducing hyperuricemic events with SGLT2 inhibitors: An updated systematic review with meta-regression

Introduction

Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) were shown to lower hyperuricemic events in patients with type 2 diabetes mellitus (T2DM), the extent of this effect in the general population is yet to be elucidated. We performed an updated systematic review and meta-analysis on a large sample of patients with and without T2DM to evaluate the influence of SGLT2i therapy on clinically relevant hyperuricemic events, defined as the composite of acute gout flare episodes, acute anti-gout management or urate-lowering therapy initiation. Furthermore, we conducted a multivariate meta-regression to assess the relationship between different covariates and the pooled effect size.

Materials and methods

We systematically searched all reported outcomes of interest in patients on SGLT2i (PROSPERO: CRD42023442077) across PubMed, Scopus and Cochrane databases looking for randomized controlled trials, observational studies and post-hoc analyses since inception until August 2023.

Results

Data from seven randomized controlled trials and seven observational studies were included for a total of 464,009 patients, 13,370 of whom did not have T2DM. A total of 50% of the patients included were on SGLT2i. The pooled analysis demonstrated that SGLT2i reduce clinically relevant hyperuricemic events by 33% (HR, 0.67; 95% CI, 0.59–0.77; I² = 83%) regardless of the concomitant diagnosis of T2DM. The multivariate meta-regression on chronic kidney disease (CKD) showed a positive correlation on the pooled effect size.

Conclusions

SGLT2i reduce the risk of developing hyperuricemic events regardless of the concomitant diagnosis of T2DM. The multivariate meta-regression on CKD showed a significant impact on the main outcome. Further studies are essential to investigate more conclusively the extent of these beneficial effects.