Rotator cuff disease, a common musculoskeletal disorder, can lead to disability [1] and is associated with considerable direct and indirect costs [1]. A cross-sectional study conducted in the United Kingdom revealed that 28.8% of the general population sought consultation for shoulder pain and that a third of these patients had a full-thickness tear [2]; this injury thus imposed a substantial burden on primary health-care services [2]. Hence, devising strategies to prevent this disease is imperative.

Studies have indicated that patients with diabetes mellitus are at elevated risks of rotator cuff tear and rotator cuff repair requirement [3,4], likely because of impaired microcirculation and nonenzymatic glycosylation [5]. A meta-analysis reported that the risk of tendon rupture was lower among individuals receiving sodium-glucose cotransporter 2 inhibitors (SGLT2is) than among those receiving placebo drugs [6]. Another meta-analysis indicated that the risk of tendonitis was higher among patients receiving an active control than among those receiving SGLT2is [7]. However, the precise mechanisms underlying these associations remain unclear. Nevertheless, this paper proposes three mechanisms that potentially mediate the protective effects of SGLT2is: anti-inflammation, weight loss, and glucose level reduction. SGLT2is boost systemic anti-inflammatory effects by increasing fat utilization, modulating macrophage-mediated inflammatory pathways [8], and inducing low-grade ketonemia [9]. Tendon tissue degeneration–related conditions, including rotator cuff tear, have been associated with inflammation [10]. SGLT2is may protect against rotator cuff tear and subsequent repair by alleviating inflammation in rotator cuff tissue. In addition, certain antidiabetic medications, such as SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), may induce weight loss [11]. Among these drugs, two common GLP-1 RAs, namely semaglutide and tirzepatide, exhibited the highest efficacy in causing weight loss [11]. Given that body mass index (BMI) is positively correlated with the incidence of rotator cuff tear [12], SGLT2i and GLP-1 RA-induced weight loss may reduce this incidence.

We compared SGLT2is with GLP-1 RAs to adjust for the confounding effects of treatment indication because both SGLT2is and GLP-1 RAs are prescribed to patients with comorbidities similar to type 2 diabetes mellitus (T2DM), including atherosclerotic cardiovascular diseases, chronic kidney disease, and obesity [11]. In the present observational study, a new-user, active comparator design was adopted to compare the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery between SGLT2i users and GLP-1 RA users. We hypothesized that SGLT2is would be more strongly associated with reduced risks of rotator cuff tear and risks of receiving repair surgery than would be GLP-1 RAs and that the protective effects of SGLT2is might derive from their anti-inflammatory effects on tendon tissues.