• Zhaohua Zhu, Jing-Yang Huang, Guangfeng Ruan, Peihua Cao, Shibo Chen, Yan Zhang, Weiyu Han, Tianyu Chen, Xiaoyan Cai, Jia Liu, Yujin Tang, Na Yu, Qian Wang, David J Hunter, James Cheng-Chung Wei, and Changhai Ding.
• Clinical Research and Orthopedic Centres (Zhu, Cao, S. Chen, Zhang, Han, T. Chen, Wang, Hunter, Ding), Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Medical Research (Huang), Chung Shan Medical University Hospital; Institute of Medicine (Huang, Wei), Chung Shan Medical University, Taichung, Taiwan; Clinical Research Centre (Ruan), Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China; Department of Rheumatology (Cai, Ding), Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China; Department of Orthopedics (Liu, Tang, Ding), Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Guangzhou Eighth People's Hospital (Yu), Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Rheumatology (Hunter), Royal North Shore Hospital and Sydney Musculoskeletal Health, Kolling Institute, University of Sydney, Sydney, Australia; Department of Medicine (Wei), Chung Shan Medical University Hospital; Graduate Institute of Integrated Medicine (Wei), China Medical University; Department of Medical Research (Wei), Taichung Veterans General Hospital, Taichung, Taiwan; Menzies Institute for Medical Research (Ding), University of Tasmania, Hobart, Australia.
• CMAJ. 2022 Dec 19; 194 (49): E1672E1684E1672-E1684.

BackgroundIt is uncertain whether metformin use is associated with reduced risk of joint replacement in patients with type 2 diabetes mellitus. We aimed to establish whether metformin use was associated with a reduced risk of total knee replacement (TKR) or total hip replacement (THR) among these patients.MethodsWe selected patients with type 2 diabetes mellitus that was diagnosed between 2000 and 2012 from the Taiwan National Health Insurance Research Database. We used prescription time-distribution matching and propensity-score matching to balance potential confounders between metformin users and nonusers. We assessed the risks of TKR or THR using Cox proportional hazards regression.ResultsWe included 20 347 participants who were not treated with metformin and 20 347 who were treated with metformin, for a total of 40 694 participants (mean age 63 yr, standard deviation 11 yr; 49.8% were women) after prescription time-distribution matching. Compared with participants who did not use metformin, those who used metformin had lower risks of TKR or THR (adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.60-0.81 for TKR or THR; adjusted HR 0.71, 95% CI 0.61-0.84 for TKR; adjusted HR 0.61, 95% CI 0.41-0.92 for THR) after adjustment for covariates. Propensity-score matching analyses (10 163 participants not treated with metformin v. 10 163 treated with metformin) and sensitivity analyses using inverse probability of treatment weighting and competing risk regression showed similar results.InterpretationMetformin use in patients with type 2 diabetes mellitus was associated with a significantly reduced risk of total joint replacement. Randomized controlled clinical trials in patients with osteoarthritis are warranted to determine whether metformin is effective in decreasing the need for joint replacement.© 2022 CMA Impact Inc. or its licensors.

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