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

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.

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.

References

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.