ArticleFrontiers in pharmacology2026
Antecedent glucagon-like peptide-1 receptor agonist use and risk of sepsis-induced cardiomyopathy in type 2 diabetes: a United States real-world active-comparator cohort study.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Sepsis-induced cardiomyopathy (SICM) is an important cardiovascular complication of infection and sepsis, particularly in patients with type 2 diabetes mellitus (T2DM). Whether antecedent glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is associated with lower SICM risk remains unclear. Methods: We conducted a retrospective active-comparator cohort study using the TriNetX United States federated electronic health record network from 1 January 2010, to 30 November 2025. Adults with T2DM and documented infection were classified according to antecedent GLP-1 RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) exposure before the index infection date and matched 1:1 by propensity score. The primary outcome was 1-year EHR-ascertained SICM or SICM-related cardiac dysfunction, defined using diagnostic codes for acute pulmonary edema, heart failure, cardiogenic shock, or cardiomyopathy, or objective cardiac dysfunction. Results: Among 189,156 eligible patients, propensity-score matching yielded 62,267 patients in each group. Over 1 year, EHR-ascertained SICM or SICM-related cardiac dysfunction occurred in 2,503 patients (4.0%) in the GLP-1 RA group and 3,059 patients (4.9%) in the DPP-4i group (HR 0.82, 95% CI 0.78-0.87; P < 0.001; E-value 1.7). GLP-1 RA use was also associated with lower risks of surrogate cardiac dysfunction (HR 0.70, 95% CI 0.64-0.76), systolic SICM (HR 0.85, 95% CI 0.77-0.93), diastolic SICM (HR 0.88, 95% CI 0.81-0.95), hyperdynamic SICM (HR 0.82, 95% CI 0.71-0.95), new-onset heart failure (HR 0.85, 95% CI 0.80-0.89), and all-cause mortality (HR 0.64, 95% CI 0.60-0.68), but not right ventricular dysfunction SICM. Negative control outcomes showed null associations, and landmark analyses were consistent. Conclusion: In this United States real-world active-comparator cohort study, antecedent GLP-1 RA exposure was associated with a lower 1-year risk of EHR-ascertained SICM or SICM-related cardiac dysfunction compared with antecedent DPP-4i exposure. These findings were consistent across sensitivity analyses and support further prospective investigation into the relationship between antecedent GLP-1 RA exposure and cardiovascular vulnerability after infection.
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