Metformin repurposing in gout: enhancing febuxostat efficacy through anti-inflammatory and metabolic modulation: a randomized controlled double-blind study

BACKGROUND: Gout is a chronic inflammatory disorder characterized by recurrent painful flares and elevated uric acid levels. Metformin possesses anti-inflammatory and metabolic regulatory properties that may offer additional benefit when combined with febuxostat. AIM: To evaluate the therapeutic efficacy of adding metformin to febuxostat in patients with gout. METHODS: A randomized, double-blinded, controlled clinical trial was conducted on 60 gout patients and were randomly assigned to receive either febuxostat and placebo (control group, n = 30) or febuxostat plus metformin (metformin group, n = 30). Clinical assessment included the visual analogue scale (VAS) for pain, while laboratory evaluation comprised serum uric acid, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and free fatty acids. All biomarkers except free fatty acids were measured using ELISA; free fatty acids were determined colorimetrically. Lipid profile parameters were also recorded. Adverse effects were monitored in both groups. RESULTS: Both groups showed significant reduction in all measured markers. The addition of metformin resulted in significantly greater reductions in VAS scores (- 33.3%), TNF-α (- 45.3%), IL-1β (- 12.3%), and uric acid levels (- 12.5%) compared with control group (all p < 0.05). The metformin group also demonstrated a significant decrease in free fatty acids (- 6.2%) with p = 0.032 and triglycerides (- 10.6%) with p = 0.002. No significant differences were observed regarding the frequency of drug-related side effects (all p > 0.05). CONCLUSION: Metformin as an adjuvant to febuxostat provides superior improvement in pain, inflammatory markers, uric acid levels, and metabolic parameters in gout patients, without increasing adverse effects.