A higher rate of knee replacement procedures was observed among people with type 2 diabetes mellitus (T2DM) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. This large retrospective cohort analysis, published in Diabetes & Metabolic Syndrome: Clinical Research & Reviews, evaluated 564,622 individuals with T2DM, including 282,311 SGLT2 inhibitor users and an equal number of non-users. 

Cox proportional hazards models were applied to evaluate the association between SGLT2 inhibitor use and TKR risk, adjusting for age, sex, Diabetes Complications Severity Index (DCSI), comorbidities, and concurrent antidiabetic therapies.

The analysis showed that SGLT2 inhibitor use was associated with a higher likelihood of undergoing TKR compared with non-use (adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI]: 1.25-1.42; p < 0.001). The incidence rate was 2.93 per 1,000 person-years among users versus 2.33 among non-users.

These findings reflect an observed association within an observational framework and may be influenced by residual confounding despite multivariable adjustment. Overall, SGLT2 inhibitor use was associated with a higher rate of TKR in this population with T2DM.