Real-world data were analyzed to evaluate the incidence and risk of sarcopenia for canagliflozin compared with other antihyperglycemic agents (AHAs) including dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), empagliflozin, and dapagliflozin.

This retrospective cohort analysis of patients with type 2 diabetes mellitus (T2DM) included new users of canagliflozin or the AHAs (2016 to 2023) in 7 United States healthcare databases. Large-scale regularized regression generated propensity scores (PS) were used for matching and controlling confounding. A conditional Cox proportional hazards model assessed the treatment effect, presented as hazard ratios (HR). A self-controlled case series (SCCS) analysis assessed the incidence rate ratio between exposed and non-exposed periods among canagliflozin users.

The PS-matched analyses showed no statistically significant increased risk of sarcopenia with canagliflozin versus any AHA comparator, though confidence intervals (CIs) were wide due to low event rates. The calibrated HRs (95 % CI) were 0.71 (0.26, 1.91) for canagliflozin versus empagliflozin, 1.16 (0.28, 4.70) for canagliflozin versus dapagliflozin, 8.79 (0.66, 116.96) for canagliflozin versus GLP-1RAs, and 0.88 (0.26, 2.98) for canagliflozin versus DPP-4 inhibitors. The crude incidence rates of sarcopenia (per 10,000 person-years) varied across databases: canagliflozin (0.0 to 1.0), dapagliflozin (0.4 to 7.9), empagliflozin (0.7 to 3.4), DPP-4 inhibitors (0.4 to 4.8), and GLP-1RAs (0.5 to 3.4). The SCCS analysis indicated an incidence ratio of 0.83 (0.50, 1.37).

The incidence rates of sarcopenia were low among patients with T2DM treated with canagliflozin or other comparator AHAs. There is no evidence suggesting an increased risk of sarcopenia associated with canagliflozin compared with other AHAs.