Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

Chieh-Hua Lu,Wu-Chien Chien,Chien-Hsing Lee,Chang-Huei Tsao,Chang-Hsun Hsieh,Yi-Jen Hung,Fu-Huang Lin,Chi-Hsiang Chung,Po-Shiuan Hsieh,Stephen L Atkin

doi:10.1371/journal.pone.0191242

Chieh-Hua Lu, Wu-Chien Chien + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0191242

Copy DOI

Abstract

BackgroundOsteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone.MethodsIn total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up.ResultsAt the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601–0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without.ConclusionsPatients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy.

Highlights

Osteoarthritis(OA) is the most common form of arthritis and possesses marked variability of disease expression
968 subjects with OA and type 2 diabetes mellitus (T2DM) under COX-2 inhibitor and metformin therapy between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender, age, and index year-controls matched without metformin therapy in this study
[6] Insulin resistance(IR) and T2DM seemed to be associated with OA in the Ulm OA and ROAD studies. [7, 8]http://rmdopen.bmj.com/ content/1/1/e000077-ref-8 In addition, the link between the two diseases may be supported by the accumulation of advanced glycation end products, oxidative stress and promotion of systemic inflammation. [9, 10] one recent meta-analysis highlights a high frequency of OA in patients with T2DM and an association between both diseases. [11]

Summary

Introduction

Osteoarthritis(OA) is the most common form of arthritis and possesses marked variability of disease expression. [14, 15] In patients with comorbidities such as T2DM, hypertension, previous gastrointestinal bleeding and advanced age, a cyclooxygenase (COX)-2 selective NSAID should be better than NSAIDs. One meta-analysis enhanced that OA treatment with celecoxib was significantly improved than that with placebo. [21] No previous study reported combination metformin and COX-2 inhibitor therapy in OA comorbid with T2DM associated with lower joint replacement surgery rate than used COX-2 inhibitor only. Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone

Objectives

Methods

Conclusion