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.