Metformin use and risk of total joint replacement in patients with diabetes: a longitudinal cohort study of Alberta's Tomorrow Project.

Abstract

Purpose: To characterize the association between metformin use and risk of total joint replacement in patients with diabetes using data from Alberta's Tomorrow Project (ATP), a population-based cohort study of chronic diseases in Alberta, Canada.

Methods: The ATP participants with incidence of diabetes after enrollment were included and followed up to March 31, 2021. Metformin use, including daily doses, was measured by a time-varying approach during the follow-up. A multivariable Cox regression model was used to characterize the association between metformin use and risk of total joint replacement, after controlling for time-related variation in drug use, clinical status, BMI, lifestyles and concurrent medications.

Results: Among 3,001 incident cases of diabetes (52% females, age at diagnosis 61.3 ± 9.5 years, average follow-up of 7.3 ± 4.7 years), the rate of total joint replacement was 7.57 per 1,000 person-year (PY) for metformin users and 9.31 per 1,000 PY for non-metformin users, with rate ratio = 0.81 (95% CI = 0.59-1.11, p-value = 0.09). In multivariable Cox regression analysis, metformin use was not significantly associated with risk of total joint replacement, with hazard ratio of 0.74 (95% CI = 0.52-1.03, p-value = 0.07) for patients with metformin medication, HR = 0.75 (95% CI = 0.46-1.22) for 0-1.0 g/day metformin use, and HR = 0.73 (95% CI = 0.49-1.08) for 1.0 + g/day use ('no metformin use' as the reference group).

Conclusions: Although our findings are not statistically significant, our study suggests clinically a potential benefit of metformin use in reducing risk of total joint replacement in patients with diabetes.