What is the clinical evidence from this study?

Study design: Observational. Population: Pulmonary Hypertension. Intervention: GLP-1 agonists vs. Sham. Primary outcome: mean pulmonary artery pressure (mPAP) (p=<0.01).

What does this research mean for the field?

GLP-1 agonists significantly reduce right ventricular dysfunction and improve mitochondrial dynamics in pulmonary hypertension models by inhibiting the GSK3β-Drp1 signaling pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to investigate the effects of GLP-1 agonist semaglutide on right ventricular dysfunction in pulmonary hypertension.

January 10, 2026European journal of medical research0 citationsOpen Access

GLP-1 agonists reduce right ventricular mitochondrial dysfunction by inhibiting the GSK3β-Drp1 signalling in pulmonary hypertension

Q: What are the key findings of this study?

GLP-1 agonists significantly reduced mPAP in a pulmonary hypertension model compared to Sham.

Q: What does this research mean for the field?

GLP-1 agonists significantly reduce right ventricular dysfunction and improve mitochondrial dynamics in pulmonary hypertension models by inhibiting the GSK3β-Drp1 signaling pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

The research aims to investigate the effects of GLP-1 agonist semaglutide on right ventricular dysfunction in pulmonary hypertension.

LZLin ZhaoCentral South University YLYanghong LiuCentral South University ZOZiwei OuCentral South University

Key Result

GLP-1 agonists significantly reduced mPAP in a pulmonary hypertension model compared to Sham.

Key Points

The research aims to investigate the effects of GLP-1 agonist semaglutide on right ventricular dysfunction in pulmonary hypertension.
Evaluated semaglutide in rodent models of pulmonary hypertension
Assessed right ventricular function using echocardiographic parameters
Performed histological analysis for RV hypertrophy and fibrosis
Analyzed GSK3β-Drp1 signalling and mitochondrial dynamics in cardiomyocytes
Semaglutide reduced right ventricular systolic pressure, indicating improved RV function
Histological analysis revealed decreased RV hypertrophy and fibrosis
Preserved mitochondrial structure was noted in treated animals
GSK3β-Drp1 signalling was restored, improving mitochondrial function

Study Design

Type

Observational

Multicenter

Structured PICO

Does the GLP-1 agonist semaglutide improve right ventricular function and mitigate mitochondrial dysfunction in rodent models of pulmonary hypertension?

Population

Adult male Sprague-Dawley (SD) rats weighing 250-300 g with right ventricular (RV) dysfunction induced by pulmonary artery banding (PAB), and neonatal rat primary cardiomyocytes.

Intervention

Semaglutide 0.052 mg/kg/day administered subcutaneously for 4 weeks (starting 4 weeks after PAB) in vivo; Semaglutide 100 nM in vitro.

Comparator

Untreated PAB rats and sham-operated control rats (in vivo); Ang II-stimulated cardiomyocytes without semaglutide (in vitro).

Outcome

Right ventricular function and structure, including right ventricular systolic pressure (RVSP), hypertrophy index (RV/LV + S), right ventricular end-diastolic area (RVEDA), right ventricular fractional area change (RVFAC), and tricuspid annular plane systolic excursion (TAPSE).surrogate

Semaglutide mitigates right ventricular dysfunction and adverse remodeling in pulmonary hypertension models by preserving mitochondrial function via the GSK3β-Drp1 signaling pathway.

Main Result

Absolute Event Rate: 36.7% vs 17.9%

p-value: p=<0.01

Limitations

Study conducted in rats, limiting generalizability to humans.
Length of follow-up may not capture long-term effects.

Abstract

Right ventricular (RV) dysfunction is a critical complication of pulmonary hypertension (PH) with limited treatment strategies. This study evaluated the therapeutic efficacy of the GLP-1 agonist semaglutide on RV dysfunction in rodent PH models, focusing on mitochondrial dynamics and GSK3β-Drp1 signalling. Semaglutide significantly improved RV function, as evidenced by reduced right ventricular systolic pressure (RVSP), hypertrophy index (RV/LV + S), and improved echocardiographic parameters (RVEDA, RVFAC, TAPSE). Histological analysis revealed reduced RV hypertrophy and fibrosis, along with preserved mitochondrial ultrastructure in semaglutide-treated PH animals. Semaglutide restored GSK3β-Drp1 signalling, maintained mitochondrial membrane potential, and decreased mitochondrial fragmentation in primary cardiomyocytes via GLP-1R activation. Modulation of GSK3β expression further confirmed its role in GLP-1’s protective effects. These findings collectively suggest that GLP-1 agonists, such as semaglutide, may represent a novel therapeutic strategy for RV dysfunction by targeting mitochondrial pathology and restoring critical signalling pathways like GSK3β-Drp1.

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