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

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.