---
title: "GLP-1 Receptor Agonists and Pulmonary Hypertension: Mechanistic Rationale and Evidence Gaps"
id: "pubmed-42747605"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42747605"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42747605/"
doi: "10.1007/s00408-026-00939-2"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# GLP-1 Receptor Agonists and Pulmonary Hypertension: Mechanistic Rationale and Evidence Gaps
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42747605
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42747605/)
- **DOI:** [10.1007/s00408-026-00939-2](https://doi.org/10.1007%2Fs00408-026-00939-2)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Pulmonary hypertension (PH) commonly coexists with **type 2 diabetes**, **obesity**, and **HFpEF**, particularly in WSPH Group 2 disease. GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists have beneficial cardiometabolic, anti-inflammatory, and vascular effects that could plausibly affect pulmonary vascular disease. - A structured narrative review (PubMed/MEDLINE and Google Scholar through March 2026) screened 491 unique records, assessed 189 full texts plus 40 supplemental references, and included 67 publications for synthesis. - **GLP-1 receptor** expression has been demonstrated in pulmonary arterial smooth muscle in human and non-human primates and in selected alveolar cell types in rodents; however, evidence does not show higher pulmonary versus systemic vascular smooth muscle expression. - GLP-1 signalling influences inflammatory pathways, endothelial nitric oxide biology, endothelin-1 pathways, and mitochondrial function—mechanisms relevant to pulmonary vascular remodelling and right ventricular dysfunction. - In preclinical models resembling Group 1 PAH (monocrotaline and hypoxia), **liraglutide** reduced right ventricular pressures, hypertrophy, and pulmonary vascular remodelling; **semaglutide** improved right ventricular mitochondrial and functional measures in an experimental pressure-overload model. - Human data are observational or derived indirectly from HFpEF trials, generally involve populations enriched for Group 2 or unclassified PH, and lack prespecified, catheterization-confirmed PH endpoints; therefore clinical efficacy for PH has not been established. - The review concludes current evidence supports mechanistic plausibility and a preclinical signal but not clinical efficacy; prospective studies with haemodynamic classification and standardized PH and right ventricular measures are required before considering GLP-1–based therapies for PH. - Key recommendation: future cardiometabolic and HFpEF trials should incorporate standardized PH endpoints, and dedicated prospective haemodynamic studies are needed.
## Clinical Analysis & Structured Key Points
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Bashar.alzghoul@mylrh.org.") Affiliations Expand ### Affiliations * 1 Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA. * 2 Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, FL, USA. * 3 Endocrine Division, Lakeland Regional Health, Lakeland, FL, USA. * 4 Division of Pulmonary, Critical Care and Sleep Medicine, The University of Texas at Austin, Austin, TX, USA. * 5 Division of Pulmonary, Critical Care and Sleep Medicine, Lakeland Regional Health, Lakeland, FL, USA. Bashar.alzghoul@mylrh.org. * PMID: **42747605** * DOI: [ 10.1007/s00408-026-00939-2 ](https://doi.org/10.1007/s00408-026-00939-2) Item in Clipboard Review # GLP-1 Receptor Agonists in Pulmonary Hypertension: Mechanistic Rationale, Preclinical Evidence, and Clinical Knowledge Gaps Laith Allaham et al. Lung. 2026. Show details Display options Display options Format Abstract PubMed PMID Lung Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lung%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Lung%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747605/) . 2026 Sep 16;204(1):68. doi: 10.1007/s00408-026-00939-2. ### Authors [Laith Allaham](https://pubmed.ncbi.nlm.nih.gov/?term=Allaham+L&cauthor_id=42747605)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-1 "Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA."), [Baylee King](https://pubmed.ncbi.nlm.nih.gov/?term=King+B&cauthor_id=42747605)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-1 "Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA."), [Fahiye Ali](https://pubmed.ncbi.nlm.nih.gov/?term=Ali+F&cauthor_id=42747605)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-1 "Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA."), [Ishita Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+I&cauthor_id=42747605)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-1 "Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA."), [Rajesh Metuku](https://pubmed.ncbi.nlm.nih.gov/?term=Metuku+R&cauthor_id=42747605)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-2 "Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, FL, USA."), [Isabella Nieto](https://pubmed.ncbi.nlm.nih.gov/?term=Nieto+I&cauthor_id=42747605)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-2 "Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, FL, USA."), [Andrew Lurie](https://pubmed.ncbi.nlm.nih.gov/?term=Lurie+A&cauthor_id=42747605)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-2 "Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, FL, USA."), [Farah N Amer](https://pubmed.ncbi.nlm.nih.gov/?term=Amer+FN&cauthor_id=42747605)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-3 "Endocrine Division, Lakeland Regional Health, Lakeland, FL, USA."), [Raju Reddy](https://pubmed.ncbi.nlm.nih.gov/?term=Reddy+R&cauthor_id=42747605)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-4 "Division of Pulmonary, Critical Care and Sleep Medicine, The University of Texas at Austin, Austin, TX, USA."), [Bashar Alzghoul](https://pubmed.ncbi.nlm.nih.gov/?term=Alzghoul+B&cauthor_id=42747605)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42747605/#short-view-affiliation-5 "Division of Pulmonary, Critical Care and Sleep Medicine, Lakeland Regional Health, Lakeland, FL, USA. Bashar.alzghoul@mylrh.org.") ### Affiliations * 1 Department of Internal Medicine, St. Bernards Medical Center, Jonesboro, AR, USA. * 2 Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, FL, USA. * 3 Endocrine Division, Lakeland Regional Health, Lakeland, FL, USA. * 4 Division of Pulmonary, Critical Care and Sleep Medicine, The University of Texas at Austin, Austin, TX, USA. * 5 Division of Pulmonary, Critical Care and Sleep Medicine, Lakeland Regional Health, Lakeland, FL, USA. Bashar.alzghoul@mylrh.org. * PMID: **42747605** * DOI: [ 10.1007/s00408-026-00939-2 ](https://doi.org/10.1007/s00408-026-00939-2) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Pulmonary hypertension (PH) frequently coexists with type 2 diabetes mellitus, obesity, and heart failure with preserved ejection fraction (HFpEF), particularly in World Symposium on Pulmonary Hypertension (WSPH) Group 2 disease. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists improve several cardiometabolic conditions and have anti-inflammatory and vascular effects. Whether these agents directly modify pulmonary haemodynamics or clinical outcomes in PH remains unknown. **Methods:** A structured narrative review was conducted using PubMed/MEDLINE and Google Scholar from database inception through March 2026, with additional studies identified by reference-list screening. Search terms encompassed GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, pulmonary hypertension, pulmonary vascular remodelling, endothelial dysfunction, inflammation, and HFpEF. The structured search yielded 491 unique PubMed/MEDLINE records. Of these, 189 were assessed at full-text level alongside 40 additional articles identified through reference-list screening; 67 publications were included in the final synthesis. Evidence was organized by mechanism, experimental model, WSPH group, and whether PH evidence was direct or indirect. **Results:** GLP-1 receptor expression has been demonstrated in pulmonary arterial smooth muscle in human and non-human primate tissue and in selected alveolar cell populations in rodent studies; however, available studies do not establish greater expression in pulmonary than systemic vascular smooth muscle. GLP-1 receptor signalling modulates inflammatory, endothelial nitric oxide, endothelin-1, and mitochondrial pathways relevant to PH. In monocrotaline- and hypoxia-induced models that primarily resemble Group 1 pre-capillary pulmonary arterial hypertension (PAH), liraglutide reduced right ventricular pressures or hypertrophy and pulmonary vascular remodelling, while semaglutide improved right ventricular mitochondrial and functional measures in an experimental pressure-overload model. By contrast, available human evidence is observational or derived indirectly from HFpEF studies, involves populations likely enriched for Group 2 or unclassified PH, and lacks prespecified, catheterization-confirmed PH endpoints. Consequently, these studies do not establish that GLP-1-based therapy prevents or treats PH. **Conclusions:** Current evidence supports a mechanistic hypothesis and a preclinical signal, not clinical efficacy in PH. Future cardiometabolic and HFpEF trials should incorporate standardized PH and right ventricular measures, and dedicated prospective studies with haemodynamic classification are required before GLP-1-based therapies can be considered for PH. **Keywords:** Cardiometabolic disease; GLP-1 receptor agonists; Heart failure with preserved ejection fraction; Inflammation; Pulmonary hypertension; Pulmonary vascular remodelling. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of interest: The authors declare no conflicts of interest relevant to the content of this review. No external funding was received for the preparation of this manuscript. All authors have read and approved the final version. ## References 1. 1. Marso SP, Daniels GH, Brown-Frandsen K et al (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375(4):311–322. - [DOI](https://doi.org/10.1056/nejmoa1603827) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/27295427/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4985288/) 2. 1. McGuire DK, Marx N, Mulvagh SL et al (2025) Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med 392(20):2001–2012. - [DOI](https://doi.org/10.1056/nejmoa2501006) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40162642/) 3. 1. Lincoff AM, Brown-Frandsen K, Colhoun HM et al (2023) Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 389(24):2221–2232. - [DOI](https://doi.org/10.1056/nejmoa2307563) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37952131/) 4. 1. Gerstein HC, Colhoun HM, Dagenais GR et al (2019) Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394(10193):121–130. - [DOI](https://doi.org/10.1016/s0140-6736\(19\)31149-3) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/31189511/) 5. 1. Perkovic V, Tuttle KR, Rossing P et al (2024) Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med 391(2):109–121. - [DOI](https://doi.org/10.1056/nejmoa2403347) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38785209/) Show all 67 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747605/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747605/) * Gastric Inhibitory Polypeptide / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gastric+Inhibitory+Polypeptide%2Ftherapeutic+use%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gastric+Inhibitory+Polypeptide) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747605/) * Glucagon-Like Peptide-1 Receptor / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glucagon-Like+Peptide-1+Receptor%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glucagon-Like+Peptide-1+Receptor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42747605/) * Glucagon-Like Peptide-1 Receptor Agonists* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glucagon-Like+Peptide-1+Receptor+Agonists%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?t
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