Effects of GLP ‐1 Receptor Agonists on Hyperuricemia, Serum Uric Acid and Gout: A Systematic Review and Meta‐Analysis

Objectives Hyperuricemia and gout are common but underappreciated comorbidities in Type 2 diabetes (T2D), obesity and chronic kidney disease (CKD). We aimed to quantify the pooled effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 receptor agonists on serum uric acid (SUA), incident gout and hyperuricemia, and to determine whether these effects vary by drug class and are mediated by weight loss. Methods We searched PubMed/MEDLINE, Embase, CENTRAL and ClinicalTrials.gov through July 2026 for RCTs of ≥ 12 weeks' duration reporting SUA change, gout flares or hyperuricemia incidence. Random‐effects meta‐analysis, subgroup and sensitivity analyses and meta‐regression were performed. Registered with PROSPERO (CRD420261468511). Results Eighteen RCTs (77 942 participants) met inclusion criteria. Incretin‐based therapy significantly reduced SUA versus control (weighted mean difference [WMD] −0.44 mg/dL, 95% CI −0.52 to −0.35), reduced incident gout flares (hazard ratio [HR] 0.62, 95% CI 0.53–0.72), and reduced hyperuricemia incidence (odds ratio [OR] 0.61, 95% CI 0.53–0.70). Dual GIP/GLP‐1 RA (tirzepatide) produced greater SUA lowering than mono GLP‐1 RAs (−0.62 vs. −0.35 mg/dL, p = 0.001). Body‐weight loss was a significant moderator of SUA reduction ( β = −0.041 mg/dL per kg, p < 0.001), explaining 84.7% of between‐trial heterogeneity, with a significant weight‐independent intercept (−0.19 mg/dL, p < 0.001). The SUA reduction was robust in all sensitivity analyses, including restriction to placebo‐controlled trials. GRADE certainty was high for SUA and moderate for gout flares (owing to small‐study effects) and hyperuricemia incidence. Conclusion Incretin‐based therapies were associated with modest reductions in SUA and with a lower incidence of gout flares and hyperuricemia, an effect largely related to weight loss. The clinical relevance of these effects, and the mechanism of any weight‐independent component, remains uncertain and warrant confirmation in dedicated trials.