Joint Replacement Rates in OA With Diabetes: Effects of COX-2 Inhibitors Plus Metformin

knee arthroscopy orthopedic surgery
knee arthroscopy orthopedic surgery
The effects of combination COX-2 inhibitor therapy with metformin on joint replacement rates were examined in patients with osteoarthritis and diabetes.

Patients with osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) who take a combination of cyclooxygenase-2 (COX-2) inhibitors and metformin have lower joint replacement surgery rates than those taking a COX-2 inhibitor alone, according to a nationwide, population-based study published in PLoS One.1

Although the mechanisms are unknown, patients with T2DM are at higher risk of developing OA compared with those without diabetes, and COX-2 inhibitors have demonstrated efficacy in significantly improving joint pain.1-3 Metformin is often used as the initial pharmacological treatment for T2DM and has been shown to reduce chronic inflammation.1,4,5 However, no previous studies have examined the effect of a combination of COX inhibitors and metformin on joint replacement surgery rates in patients with T2DM and OA.1

Therefore, researchers used data from the Taiwan National Health Insurance Research Database to compare the effects of combined metformin and COX-2 inhibitor therapy (n=968) vs COX-2 therapy alone (n=1936) on joint replacement rates during a 10-year period. At the end of follow-up, they found that 124 (12.81%) patients in the combination therapy group and 314 (16.22%) patients in the COX-2 inhibitor-only group had undergone joint replacement surgery.

Even after adjusting for comorbidities and other covariates, analyses demonstrated that patients receiving combination therapy had a significantly lower 10-year risk for joint replacement surgery compared with patients receiving COX inhibitors alone. This lower risk may be attributable to a decrease in pro-inflammatory factors from combination therapy compared with patients not taking metformin; however, the mechanisms responsible for this association are unclear.

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The authors concluded that, “Combination COX-2 inhibitors and metformin therapy in OA patients with T2DM are associated with lower joint replacement surgery rates than COX-2 inhibitor alone.”1 Further studies are needed on the effects in reducing the joint replacement surgery risk for OA in patients with T2DM.


  1. Lu C-H, Chung C-H, Lee C-H, et al. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan. PLoS ONE. 2018;13(1):e0191242.
  2. Louati K, Vidal C, Berenbaum F, Sellam J. Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis. RMD Open. 2015;1(1):e000077.
  3. Xu C, Gu K, Yasen Y, Hou Y. Efficacy and safety of celecoxib therapy in osteoarthritis: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016; 95(20):e3585.
  4. Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2017;166(8):572-578.
  5. Diaz A, Romero M, Vazquez T, Lechner S, Blomberg BB, Frasca D. Metformin improves in vivo and in vitro B cell function in individuals with obesity and type-2 diabetes. Vaccine. 2017;35(20):2694-2700.