Metformin Use Is Associated With Reduced Inflammation and Pain After Total Knee Arthroplasty in Patients With Type 2 Diabetes

OBJECTIVE: Postoperative inflammation and pain remain key barriers to recovery after total knee arthroplasty (TKA). Metformin has anti-inflammatory properties, but its perioperative impact in TKA is unclear. This study evaluated whether regular metformin use reduces postoperative inflammation and pain in T2DM patients undergoing TKA. METHODS: In this single-center retrospective cohort study, patients with Type 2 diabetes mellitus (T2DM) who underwent primary TKA between December 2024 and May 2025 were included. Patients were grouped based on whether they had regularly taken metformin. 1:1 propensity score matching was performed to reduce baseline differences between groups, yielding 60 matched pairs. Inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and D-dimer were measured preoperatively and on postoperative days 1 and 3. Pain was assessed using the Visual Analogue Scale (VAS) on postoperative days 1 and 3. Linear mixed-effects models were used to compare outcomes between groups after adjusting for residual confounders. RESULTS: In the matched cohort, the metformin group showed significantly lower CRP levels on postoperative day 3 (107.04 ± 49.19 vs. 130.91 ± 59.62 mg/L, p = 0.02), lower IL-6 levels on postoperative day 1 (62.22 ± 47.17 vs. 91.07 ± 41.55 pg/mL, p < 0.01), and postoperative day 3 (31.33 ± 20.84 vs. 57.74 ± 59.98 pg/mL, p < 0.01), and lower ESR levels on postoperative day 3 (45.40 ± 17.85 vs. 47.05 ± 20.19 mm/h, p = 0.03) than the non-metformin group. VAS pain scores on postoperative day 3 were also significantly lower in the metformin group (3.03 ± 1.03 vs. 4.15 ± 1.25, p < 0.01). These differences remained significant after adjusting for confounders. CONCLUSION: Long-term regular use of metformin is associated with reduced acute inflammation and postoperative pain in T2DM patients undergoing TKA. As a widely used and well-tolerated medication, metformin holds promise as a low-cost, adjunctive therapeutic strategy to enhance early recovery and improve perioperative outcomes in diabetic patients undergoing TKA.