Metformin Reduces the Incidence of Shoulder Stiffness After Arthroscopic Rotator Cuff Repair: A Randomized, Double-Blinded, Placebo-Controlled Trial

Background: Shoulder stiffness after arthroscopic rotator cuff repair (RCR) is associated with a prolonged rehabilitation process and impaired functional outcomes. Previous studies have demonstrated that metformin can alleviate joint stiffness in animal models. However, its clinical effectiveness and safety require further confirmation in clinical practice. Purpose/Hypothesis: The purpose of this study was to investigate whether 3 months of postoperative treatment with metformin, compared with placebo, reduced the incidence of shoulder stiffness in patients after arthroscopic RCR. It was hypothesized that the postoperative administration of metformin would decrease the risk of postoperative shoulder stiffness. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 146 consecutive patients with rotator cuff tears were randomly assigned to receive a 500-mg dose of metformin or placebo twice daily for 3 months after arthroscopic RCR. The primary outcome was the incidence of shoulder stiffness at 3 months’ follow-up. Secondary outcomes included the American Shoulder and Elbow Surgeons (ASES) score, pain, and patient satisfaction during the first postoperative year as well as concentrations of plasma fibrotic biomarkers at 3 months’ follow-up. The primary and secondary outcomes were measured at baseline and 3 months, 6 months, and 1 year postoperatively. Safety was assessed by adverse events, and rotator cuff tendon healing was evaluated by ultrasonography. Results: Complete outcome measurements were obtained for 126 patients. There were 64 participants in the metformin group and 62 in the control group. The incidence of shoulder stiffness was significantly lower in the metformin group than in the control group at 3 months postoperatively (11% vs 27%, respectively; risk ratio, 0.40 [95% CI, 0.18-0.90]; P = .02). There was no significant difference regarding ASES, pain, and satisfaction scores between groups at 1-year follow-up. The concentrations of plasma fibrotic biomarkers were significantly lower in the metformin group than in the control group. The tendon healing rates were comparable between the 2 groups at final follow-up (risk ratio, 0.97 [95% CI, 0.86-1.10]; P = .83). Conclusion: Metformin treatment reduced the incidence of shoulder stiffness after arthroscopic RCR. Metformin did not negatively influence rotator cuff tendon healing. These findings indicated that metformin is a potential pharmacological prophylaxis for postoperative shoulder stiffness. Registration: Chinese Clinical Trial Registry (ChiCTR2300074329)