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.