Key result
Prior GLP-1 RA use linked to ~18% lower sepsis-induced cardiomyopathy risk vs. DPP-4 inhibitors.
Why the study?
Whether antecedent glucagon-like peptide-1 receptor agonist use is associated with a lower risk of sepsis-induced cardiomyopathy in patients with type 2 diabetes mellitus remains unclear.
Does antecedent GLP-1 RA exposure reduce the risk of sepsis-induced cardiomyopathy in adults with type 2 diabetes and infection?
Cohort (n=124,534)
Yes
Does antecedent GLP-1 RA exposure reduce the risk of sepsis-induced cardiomyopathy in adults with type 2 diabetes and infection?
Hazard Ratio: 0.82 (95% CI 0.78–0.87)
Absolute Event Rate: 4% vs 4.9%
p-value: p=<0.001
Antecedent use of GLP-1 RAs in patients with type 2 diabetes is associated with a significantly lower 1-year risk of sepsis-induced cardiomyopathy following infection compared to DPP-4i use.
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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Wu et al. (2026) conducted a cohort in Type 2 diabetes mellitus and documented infection (n=124,534). Glucagon-like peptide-1 receptor agonist (GLP-1 RA) vs. Dipeptidyl peptidase-4 inhibitor (DPP-4i) was evaluated on 1-year EHR-ascertained sepsis-induced cardiomyopathy (SICM) or SICM-related cardiac dysfunction (HR 0.82, 95% CI 0.78-0.87, p=<0.001). Antecedent GLP-1 RA exposure was associated with an 18% lower 1-year risk of sepsis-induced cardiomyopathy compared to DPP-4i exposure in patients with type 2 diabetes and infection (HR 0.82).
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