Glucagon Like Peptide-1 Receptor Activation Attenuates Cardiac Fibrosis Biomarkers

Background: Myocardial fibrosis is a pathological process linked to adverse cardiac outcomes. Glucagon like peptide-1 receptor agonists (GLP-1 RAs), a class of anti-diabetic drugs, provide cardiovascular benefits beyond glycemic control. Preventing cardiac fibrosis in general and atrial remodeling in particular is crucial to delay cardiac disease progression. We aimed to evaluate the short-term effect of GLP-1 RA on LA reservoir strain, a reliable, noninvasive surrogate of atrial remodeling, as well as on serum levels of established cardiac fibrosis biomarkers.

Methods: Consecutive patients >18 years with obesity, prior to GLP-1 RA treatment, were included between June 2023 and June 2024. Conventional echocardiography and 2D speckle-tracking echocardiography (2D-STE) were performed at baseline and after 3 months of GLP-1 RA treatment. Plasma biomarkers of collagen synthesis (PICP and PIIINP), as well as hs-CRP were measured.

Results: Of 20 recruited patients, 12 completed the protocol (Semaglutide, n=4; Liraglutide, n=8). BMI decreased significantly from 36.75 to 35.2 kg/m² (p<0.0001), with no difference between drugs. No significant change was observed in LA reservoir strain (p=0.0693) or CRP (p=0.9692). PICP levels also did not change in the cohort (p=0.7910). However, plasma PIIINP levels decreased significantly from 66.4 to 58.2 ng/mL (p=0.0068). Liraglutide was the main contributor to this reduction (p=0.0156), while Semaglutide had no significant effect.

Conclusions: In obese individuals, GLP-1 activation significantly reduces specific cardiac fibrosis biomarkers after three months, suggesting an additional mechanism underlying its cardioprotective effects. The potential attenuation of atrial remodeling should be further investigated in larger cohorts to obtain more conclusive findings