(C-241) A Retrospective Cohort Study of Sarcopenia in Patients with Type 2 Diabetes Mellitus treated with SGLT2 Inhibitors and Other Antihyperglycemic Agents

Background: Sarcopenia, primarily age-related, is a progressive disorder characterized by the generalized loss of skeletal muscle mass and strength, leading to an increased risk of falls, physical disability, and mortality. This condition has been increasingly reported in patients with Type 2 Diabetes Mellitus (T2DM). However, the relationship between sarcopenia and antihyperglycemic agents (AHAs) remains underexplored.

Objectives: To evaluate the incidence of sarcopenia using data from routine clinical practice and to assess the association between sarcopenia and treatment with canagliflozin (cana) compared to other AHAs.

Methods: We analyzed data from seven large US databases (six health insurance claims and one electronic health record) involving adult patients with T2DM from 2016 to 2023 who were new users of either cana or comparator agents (DPP-4 inhibitors, GLP-1 receptor antagonists, empagliflozin, or dapagliflozin), forming four pairwise comparison cohorts. We employed large-scale regularized regression to derive propensity scores (PS) for matching and controlling confounding variables. Negative control outcomes were utilized to evaluate systematic errors in the study design and for empirical calibration. A conditional Cox proportional hazards model assessed the comparative treatment effect on sarcopenia through on-treatment analysis, presented as the hazard ratio (HR) based on the matched sets. Additionally, a self-controlled case series (SCCS) design was used to assess the incidence rate ratio between exposed and non-exposed periods within the cana cohort. Analyses were conducted separately within each database and subsequently combined using Bayesian random-effects meta-analysis, contingent on the comparative cohorts passing prespecified diagnostic tests.

Results: The study included approximately 0.5 million cana users and 10 million comparator users. The crude incidence rates of sarcopenia (per 10,000 person-years) varied across the databases as follows: cana (0.0 to 1.0), DPP-4 inhibitors (0.4 to 4.8), GLP-1 (0.5 to 3.4), dapagliflozin (0.4 to 7.9), and empagliflozin (0.7 to 3.4). PS-matched analyses showed no significant differences, with meta-analytical calibrated HRs (95% CI): 0.71 (0.26, 1.91) for cana vs. empagliflozin, 1.16 (0.28, 4.70) for cana vs. dapagliflozin, 8.79 (0.66, 116.96) for cana vs. GLP-1, and 0.88 (0.26, 2.98) for cana vs. DPP-4. The SCCS analysis indicated an incidence ratio of 0.83 (0.50, 1.37).

Conclusions: The incidence rates of sarcopenia were low among patients with T2DM treated with canagliflozin or other comparator AHAs. This study found no evidence suggesting an increased risk of sarcopenia associated with canagliflozin compared to other AHAs.