PT  - JOURNAL ARTICLE
AU  - Zhaohua Zhu
AU  - Jing-Yang Huang
AU  - Guangfeng Ruan
AU  - Peihua Cao
AU  - Shibo Chen
AU  - Yan Zhang
AU  - Weiyu Han
AU  - Tianyu Chen
AU  - Xiaoyan Cai
AU  - Jia Liu
AU  - Yujin Tang
AU  - Na Yu
AU  - Qian Wang
AU  - David J. Hunter
AU  - James Cheng-Chung Wei
AU  - Changhai Ding
TI  - Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study
AID  - 10.1503/cmaj.220952
DP  - 2022 Dec 19
TA  - Canadian Medical Association Journal
PG  - E1672--E1684
VI  - 194
IP  - 49
4099  - http://www.cmaj.ca/content/194/49/E1672.short
4100  - http://www.cmaj.ca/content/194/49/E1672.full
SO  - CMAJ2022 Dec 19; 194
AB  - Background: It 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.Methods: We 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.Results: We 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.Interpretation: Metformin 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.