https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Jena Klinik für Innere Medizin I - Kardiologie Jena, Deutschland; 2Universitätsklinikum Jena Institut für Medizinische Statistik, Informatik und Datenwissenschaften Jena, Deutschland
Activating the Glucagon-like peptide 1 (GLP-1) receptor has been shown to improve exercise capacity in obese patients with heart failure with preserved ejection fraction (HFpEF) but the mechanisms are incompletely understood. Furthermore, it remains unclear if these effects are obesity-dependent. Left ventricular diastolic dysfunction is a key component of HFpEF. We aimed to assess the effects of GLP-1 based treatments on diastolic function in various animal models of cardiac disorders using a meta-analytic approach.
Methods:
We searched Medline via Ovid, Scopus and Web of Science from inception until September 2024 for preclinical studies investigating the effects of GLP-1 receptor agonists or dipeptidyl peptidase 4 (DPP-4) inhibitors on left ventricular diastolic function in any model of heart disease. To enclose all available measures of diastolic function while considering hierarchical dependency, we conducted a four-level meta-analysis. We employed meta-regression to explore sources of heterogeneity and contour-enhanced funnel plot to assess publication bias. Study quality was evaluated using the CAMARADES checklist. The protocol of this work is registered in PROSPERO (CRD42023452886).
Results:
Of a total of 16912 studies screened, 57 fulfilled our inclusion criteria. Meta-analysis revealed that GLP-1 based treatments remarkably improve left ventricular diastolic function (Hedges' g = 1.08, 95% CI: 0.77 - 1.38, p < 0.01). Meta-regression showed comparable effects between GLP-1 receptor agonists (Hedges' g = 1.02, 95% CI: 0.48 - 1.56, p < 0.01) and DPP-4 inhibitors (Hedges' g = 1.11, 95% CI: 0.74 - 1.47 p < 0.01). Nevertheless, the efficacy of GLP-1 treatments on diastolic function differs among disease models. While strong treatment effects were found in diabetic cardiomyopathy (Hedges’ g = 1.56, 95% CI: 1.03 - 2.09, p < 0.001) and myocardial infarction (Hedges’ g = 1.57, 95% CI: 0.71 - 2.42, p < 0.001), changes in pressure overload-induced cardiac dysfunction were not significant. Interestingly, we found no difference in effect size between obese and non-obese models.
Conclusions:
Pharmacological activation the GLP-1 receptor may preserve left ventricular diastolic function. Their efficacy unlikely depends on drug class or the presence of obesity but may vary among etiologies of cardiac disorders. The impact of GLP-1 based treatments on diastolic function might therefore contribute to its cardioprotective effects in HFpEF irrespective of obesity.