CMAJ Study Finds Metformin Associated with Reduced Risk of Joint Replacement in Diabetic Patients What are the main findings?

Our observational study found metformin use in patients with type 2 diabetes was associated with roughly 30% risk reduction of total knee and/ or hip replacement, compared with non-users.

The adjusted hazard ratio of THR or TKR was 0.69 (95% CI 0.60-0.78) in metformin users compared with non-users, after adjusting for age, sex, diabetes severity, medications for pain management, other OAGs, and insulin use. The findings were extremely consistent using multiple regression models (PTDM, PSM, IPTW and competing risk regression models). What should readers take away from your report?

Take away message: Osteoarthritis is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and poses a challenge for the development of effective treatment on OA. There is no magic drug that can treat all the osteoarthritis patients.  The current study suggests consistent benefits of metformin use for osteoarthritis management among type 2 diabetes mellitus. The findings may stimulate future clinical trials to test the efficacy and effectiveness of metformin for osteoarthritis treatment. What recommendations do you have for future research as a result of this study?

Response: Next step would be conducting Randomized Clinical Trials to examine the effect of Metformin on osteoarthritis, particularly in overweight osteoarthritis patients. Our team has been recruiting participants for the ongoing trial “Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial” (ClinicalTrials. gov NCT05034029 . Registered on 30 Sept 2021). ||

Meanwhile, some novel anti-hyperglycemic agents, particularly GLP-1 analogues might produce similar or even better protective effects for people with OA. As far as we know, Prof. Francis Berenbaum has initiated a randomized double blind, Phase I clinical trial to evaluate the safety, tolerability and pharmacokinetics of GLP-1 analogues in the target of knee joint of OA patients. Our team has been conducting a multi-center RCT to examine the effect of metformin on overweight OA patients, which would provide high quality evidence. We are also exploring the potential protective effect of SGLT-2, Dpp4i etc in protecting OA by using Real World Data. The preliminary results will be released in March of 2023. Therefore, we hope more exciting findings can be published in the coming years and breakthrough of OA treatment would be achieved.

We have no conflict of interests to declare.


Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study Zhaohua Zhu PhD, Jing-Yang Huang PhD, Guangfeng Ruan MD, Peihua Cao PhD, Shibo Chen MMed, Yan Zhang PhD, Weiyu Han MD PhD, Tianyu Chen MD, Xiaoyan Cai MD, Jia Liu MD, Yujin Tang MD, Na Yu MD, Qian Wang MD PhD, David J. Hunter MD PhD, James Cheng-Chung Wei MD PhD, Changhai Ding MD PhD n Cite as: CMAJ 2022 December 19;194:E1672-84. doi: 10.1503/cmaj.220952

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Last Updated on December 20, 2022 by