Home Clean Living Regular metformin use slows knee osteoarthritis progression in patients with diabetes

Regular metformin use slows knee osteoarthritis progression in patients with diabetes


September 19, 2022

2 min read


The authors report receiving grant support from the Health and Medical Research Fund (HMRF) of the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region and the Research Grants Council of the Hong Kong Special Administrative Region, China.

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Patients with type 2 diabetes who report regular metformin use demonstrate a potential slowing of knee osteoarthritis progression, according to data published in Scientific Reports.

“In addition to its glucose-lowering effects in type 2 diabetes mellitus (DM), metformin also modulates inflammatory and metabolic factors, resulting in reduced inflammation and plasma lipids levels,” Francisco T. T. Lai, BSc, MPhil, PhD, of the University of Hong Kong, and co-authors wrote. “Metformin, a well-known adenosine monophosphate-activated kinase (AMPK) activator, can suppress cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA and protein expression in a dose-dependent pathway.

Infographic showing effect of metformin
Patients with type 2 diabetes who report regular metformin use demonstrate a potential slowing of knee OA progression, according to data derived from Lai FTT, et al. Scientific Reports. 2022;doi:10.1038/s41598-022-15871-7.

“Its mechanism on the reduction of pain intensity in many inflammatory disorders is explained by its inhibitory effects on the level of pro-inflammatory mediators, thus reducing the level of inflammatory cytokines including TNF-, IL-1, IL-6, IL-10 and adipokines,” they added. “The suppressed level of COX-2 and iNOS also reduces the levels of NO and PGE2 in cell culture media. The above anti-inflammatory and anti-oxidative effect of metformin on synovial joint tissue may reduce pain based on the metabolic regulation of inflammation in OA.”

To investigate the potential impact of metformin on the progression of knee OA in patients with type 2 diabetes, Lai and colleagues conducted a retrospective cohort study. The researchers extracted data from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong, which collects information from all clinical consultations as part of routine practice.

The authors received access to routine records from all patients in the public sector aged 45 years or older. Researchers then created a closed cohort consisting of all patients with type 2 diabetes who visited any Hospital Authority-run clinic between Jan. 1, 2007, and Dec. 31, 2010. After enrollment, patients were followed until being admitted to a hospital for a total knee replacement (TKR), in-hospital death, or 4 years had passed from baseline.

Patients were defined as regular metformin users if they filled four or more prescriptions in the year leading up to enrollment. The primary outcome was the incidence of the first TKR undergone in a public hospital between Jan. 1, 2011, and Dec. 31, 2014. TKR revisions were not counted as an endpoint.

The analysis consisted of a matched cohort made up of 93,330 patients, of whom half (46,665) were regular metformin users. Among the regular metformin users, 184 patients were admitted for a TKR within 4 years. In the group that did not use metformin, 222 underwent TKRs within 4 years, according to the researchers. In the Cox regression, the HR for TKR among regular metformin users, compared with non-users, was 0.81 (95% CI, 0.67-0.98).

“Despite the low incidence of TKR and a relatively short 4 years follow-up period, we found a statistically significant 19% reduction in the rate of TKR in a diabetic population who are regular metformin users compared to non-users, with an apparent dose-response relationship,” Lai and colleagues wrote. “Future research should include longitudinal studies of longer follow-up period, more specific selection of patients with preexisting diagnoses of knee OA and its severity, and include dosage information of metformin.”


Osteoarthritis: structural endpoints for the development of drugs, devices, and biological products for treatment guidance for industry. 2018. Accessed July 26, 2022.

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