Background: Inflammatory myositis, such as dermatomyositis and polymyositis, and necrotizing myopathy are distinct autoimmune muscle disorders characterized by chronic muscle damage and systemic complications. Both conditions are associated with an increased risk of cardiovascular events due to persistent systemic inflammation. GLP-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefits in diabetes with evidence of reductions in morbidity and mortality. However, their role in these conditions remains unclear.

Objectives: To investigate the impact of GLP-1 RA therapy on mortality and cardiovascular outcomes in patients with inflammatory myositis and necrotizing myopathy over three years.

Methods: Data for this retrospective cohort study were obtained from the TriNetX Global Collaborative Network. Adults aged 18 and older diagnosed with inflammatory myositis or necrotizing myopathy were identified using ICD-10 codes. The cohort with GLP-1 RA use (n = 3,066) included patients treated with Exenatide, Dulaglutide, Liraglutide, Semaglutide, Tirzepatide, or Lixisenatide, while the comparator cohort without GLP-1 RA use (n = 57,788) included patients not receiving these therapies. Propensity score matching (PSM) was conducted to adjust for baseline differences, including demographics (age, sex, ethnicity), comorbidities (hypertension, diabetes, obesity, smoking), and medication use (statins, insulin, corticosteroids, SGLT2 inhibitors, methotrexate, rituximab). GLP-1 RA use was defined as the index event, and outcomes were monitored for three years. Preexisting conditions were excluded before the index event. The outcomes assessed included all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiac arrest, venous thromboembolism (VTE), stroke, and myocarditis.

Results: Before matching, patients in the GLP-1 RA group were older (mean age 58.1 vs. 54.9 years), predominantly female (67.0% vs. 64.8%), and more likely to be white (60.1% vs. 52.7%) compared to the Non-GLP-1 RA group. Comorbidities such as hypertension (73.6% vs. 25.8%), diabetes (71.1% vs. 14.4%), and obesity were more prevalent, and medication use, including aspirin (44.2%) and metformin (56.8%), was also higher. After matching, these differences were balanced, with 2,444 patients in each group. Significant reductions in adverse outcomes were observed in the GLP-1 RA group. A summary of these findings is presented in Table 1 below. The risk of all-cause mortality was significantly lower (RR 0.367, 95% CI: 0.292–0.460, p < 0.001). The risk of MACE was marginally lower (RR 0.813, 95% CI: 0.661–0.990, p = 0.049). GLP-1 RA therapy was associated with reduced risks of myocardial infarction (RR 0.654, 95% CI: 0.464–0.924, p = 0.015), cardiac arrest (RR 0.497, 95% CI: 0.262–0.941, p = 0.028), and venous thromboembolism (RR 0.566, 95% CI: 0.412–0.779, p < 0.001). No significant differences were observed for stroke (RR 0.755, 95% CI: 0.520–1.095, p = 0.137) or myocarditis (RR 0.995, 95% CI: 0.415–2.386, p = 0.991).

Conclusion: GLP-1 RA is associated with significant reductions in mortality and cardiovascular events in patients with inflammatory myositis and necrotizing myopathy. These findings suggest that GLP-1 RAs may be a valuable adjunctive therapy for improving outcomes in these high-risk populations. Further research is needed to confirm these results and investigate underlying mechanisms.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.