Pulmonary hypertension (PH) frequently coexists with cardiometabolic disorders including type 2 diabetes mellitus, obesity, and heart failure with preserved ejection fraction (HFpEF). This association is particularly notable in World Symposium on Pulmonary Hypertension (WSPH) Group 2 disease, where left-heart disease contributes to pulmonary vascular pressure elevation. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GIP/GLP-1 receptor agonists improve several cardiometabolic outcomes and exert anti-inflammatory and vascular effects. Whether these agents directly alter pulmonary haemodynamics, pulmonary vascular remodelling, or clinical outcomes in PH has been unclear.
The authors performed a structured narrative review of the literature using PubMed/MEDLINE and Google Scholar from database inception through March 2026, supplemented by reference-list screening. The structured search identified 491 unique PubMed/MEDLINE records; 189 were assessed at full-text level, and 40 additional articles were identified by reference review. In total, 67 publications were included in the final synthesis. Evidence was organized by mechanism, experimental model, WSPH group, and whether the evidence addressing PH was direct or indirect.
Studies have demonstrated GLP-1 receptor expression in pulmonary arterial smooth muscle in human and non-human primate tissue. Rodent studies have also identified receptor expression in selected alveolar cell populations. However, available data do not establish that GLP-1 receptor expression is higher in pulmonary vascular smooth muscle than in systemic vascular smooth muscle.
GLP-1 receptor signalling modifies several biological pathways that are mechanistically relevant to PH pathogenesis, including:
Modulation of inflammatory signalling cascades that contribute to vascular remodelling.
Effects on endothelial nitric oxide pathways, which influence vascular tone and endothelial function.
Interaction with endothelin-1 signalling, a vasoconstrictive and proliferative mediator implicated in PH.
Regulation of mitochondrial pathways that affect cellular energetics and right ventricular function.
These mechanistic links provide biological plausibility for an effect of GLP-1–based therapies on pulmonary vascular disease and right ventricular adaptation.
Preclinical studies have yielded a signal suggesting potential benefit of GLP-1 receptor agonists in experimental models of pulmonary vascular disease. In monocrotaline- and hypoxia-induced models—models that primarily resemble WSPH Group 1 pre-capillary pulmonary arterial hypertension (PAH)—treatment with liraglutide was associated with reductions in right ventricular pressures or hypertrophy and attenuation of pulmonary vascular remodelling.
Separately, semaglutide improved right ventricular mitochondrial measures and functional endpoints in an experimental pressure-overload model. These findings indicate that GLP-1 receptor agonists can influence both pulmonary vascular pathology and right ventricular biology in animal systems. Nonetheless, differences between experimental models and human PH etiologies, as well as variability in dosing and timing, limit direct translational inference.
Human evidence addressing GLP-1 receptor agonists in PH is currently limited and largely indirect. Available clinical data are observational or derived from trials in HFpEF or cardiometabolic populations rather than from studies designed to assess PH. These patient populations are likely enriched for WSPH Group 2 or unclassified PH rather than Group 1 PAH.
Importantly, the human studies reviewed did not include prespecified, catheterization-confirmed PH endpoints. As a result, current clinical data do not establish that GLP-1–based therapies prevent, treat, or modify the course of PH as defined haemodynamically by right heart catheterization.
The review identifies several key knowledge gaps that must be addressed before GLP-1 receptor agonists can be considered for PH management:
Lack of haemodynamically confirmed clinical endpoints: prospective studies should include right heart catheterization or other standardized haemodynamic assessments as prespecified endpoints.
Need for standardized right ventricular measures: trials should incorporate standardized imaging, biomarker, or functional measures of right ventricular structure and function.
Clarification of target populations: future work should define which WSPH groups might benefit (for example, differentiating Group 1 PAH mechanisms from Group 2 HFpEF-associated PH).
Dose, agent, and timing: preclinical signals vary by agent (e.g., liraglutide, semaglutide) and model; optimal dosing, duration, and translational relevance require definition.
Comparative mechanistic studies: more data are needed to compare pulmonary versus systemic vascular GLP-1 receptor expression and to elucidate cell-specific signalling in human pulmonary vascular and right ventricular tissue.
The authors recommend that forthcoming cardiometabolic and HFpEF trials incorporate standardized PH and right ventricular measures, and that dedicated prospective studies with haemodynamic classification be prioritized.
Current evidence supports a mechanistic rationale and a preclinical signal for potential effects of GLP-1 receptor agonists on pulmonary vascular remodelling and right ventricular biology. However, clinical efficacy in PH has not been demonstrated. Human data to date are observational or indirect, lack prespecified haemodynamic PH endpoints, and are concentrated in populations likely enriched for Group 2 or unclassified PH. Dedicated prospective studies with haemodynamic classification and standardized right ventricular assessments are required before GLP-1–based therapies can be considered for prevention or treatment of PH.
The review synthesized 67 publications identified through the structured search and reference screening; full reference details are provided in the source article. Specific preclinical and clinical citations mentioned in the abstract include animal-model studies of liraglutide and semaglutide and multiple large cardiometabolic outcome trials cited in the reference list, but detailed reference-level outcomes and study-level data were reported in the original article and are not reproduced here.