Abstract Body (Do not enter title and authors here): Background:
Peripartum cardiomyopathy (PPCM) is a potentially fatal form of heart failure with no established targeted therapy. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in other populations, but their effects in non-diabetic PPCM patients are unknown.

Methods:
We queried the TriNetX Global Collaborative Network for women aged 18–60 diagnosed with PPCM (ICD-10: O90.3), excluding those with any diabetes (E10–E13). Patients prescribed GLP-1 RAs (liraglutide, semaglutide, exenatide, dulaglutide, lixisenatide, albiglutide) were compared to GLP-1-naïve PPCM controls. Propensity score matching (1:1) yielded 374 patients per group. Outcomes were assessed over 5 years and included hospitalization, heart failure exacerbation, mortality, and changes in left ventricular ejection fraction (LVEF).

Results:
GLP-1 RA use was associated with significantly lower hospitalization (21.1% vs. 36.6%, OR 0.46 [95% CI 0.34–0.64], p<0.001) and acute heart failure exacerbations (2.7% vs. 8.6%, OR 0.29 [0.14–0.61], p<0.001). Additional improvements were observed in shortness of breath (23.3% vs. 30.5%, p=0.026), and GLP-1 users demonstrated a lower rate of deterioration in left ventricular function (LVEF <40%: 2.7% vs. 5.9%, OR 0.44, p=0.030). Mortality was similar between groups (2.7% vs. 2.7%, OR 1.00), but GLP-1 users had significantly improved survival on Kaplan-Meier analysis (p=0.004, survival 99.7% vs. 93.7%). No significant increase was noted in AKI, pancreatitis, or myocardial infarction.

Conclusion:
In this large real-world cohort of non-diabetic PPCM patients, GLP-1 RA use was associated with reduced heart failure events, improved LVEF, and better survival over 5 years without increased adverse events. These findings support further investigation into GLP-1 RAs as a potential cardioprotective therapy in PPCM.