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; Chi-Hsiang Chung; Chien-Hsing Lee; Chang-Hsun Hsieh; Yi-Jen Hung; Fu-Huang Lin; Chang-Huei Tsao; Po-Shiuan Hsieh; Wu-Chien Chien

doi:10.1371/journal.pone.0191242

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 Jan 31;13(1):e0191242. doi: 10.1371/journal.pone.0191242. eCollection 2018.

Authors

Chieh-Hua Lu^{1

2}, Chi-Hsiang Chung^{3

4}, Chien-Hsing Lee¹, Chang-Hsun Hsieh¹, Yi-Jen Hung¹, Fu-Huang Lin³, Chang-Huei Tsao^{5

6}, Po-Shiuan Hsieh^{2

7

8}, Wu-Chien Chien^{2

3}

Affiliations

¹ Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
² Department of Medical Research, National Defense Medical Center, Taipei, Taiwan, ROC.
³ School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
⁴ Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan, ROC.
⁵ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
⁶ Department of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan, ROC.
⁷ Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
⁸ Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.

Abstract

Background: Osteoarthritis (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.

Methods: In 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.

Results: At 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.

Conclusions: Patients 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Arthroplasty, Replacement* / statistics & numerical data
Cohort Studies
Cyclooxygenase 2 Inhibitors / administration & dosage*
Diabetes Mellitus, Type 2 / complications*
Diabetes Mellitus, Type 2 / drug therapy*
Drug Therapy, Combination
Female
Humans
Hypoglycemic Agents / administration & dosage*
Male
Metformin / administration & dosage*
Middle Aged
Osteoarthritis / complications*
Osteoarthritis / drug therapy*
Osteoarthritis / surgery
Proportional Hazards Models
Retrospective Studies
Taiwan

Substances

Cyclooxygenase 2 Inhibitors
Hypoglycemic Agents
Metformin

Grants and funding

This study was funded by Tri-Service General Hospital Research and Medical Affairs Bureau, Ministry of National Defense Foundation (TSGH-C104-122, MAB-105-07, TSGH- C106-002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.