Impact of metformin on the risk of osteoarthritis in patients with type 2 diabetes: a real-world study.

AIMS: To investigate the association between metformin use and osteoarthritis (OA) risk or total knee replacement (TKR) need in type 2 diabetes (T2DM) patients, addressing limited real-world evidence on metformin's potential joint-protective effects.

METHODS

This retrospective cohort study analyzed electronic health records (January 2015-December 2021) from a large healthcare database. We identified 244,562 metformin users and 117,529 non-users with T2DM. Multivariable-adjusted Cox proportional hazards models evaluated OA development and TKR risk, with propensity score matching and competing risk models minimizing confounding.

RESULTS

Among 362,091 patients, 28,724 incident OA cases and 1,593 TKR procedures occurred. Metformin users showed significantly reduced OA risk versus non-users (adjusted HR 0.95, 95% CI 0.92-0.96, p < 0.001). No significant TKR risk difference was observed (adjusted HR 1.05, 95% CI 0.94-1.18, p = 0.352). Results remained robust through sensitivity analyses including propensity score matching and competing risk regression.

CONCLUSION

In this large real-world T2DM cohort, metformin use associated with modestly reduced OA incidence but unchanged TKR risk. These findings support preclinical and clinical evidence for metformin's potential protective role against OA development.