The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease

Wang, Wenwen; Mei, Aihua; Qian, Hang; Li, Dongfeng; Xu, Hui; Chen, Jishun; Yang, Handong; Min, Xinwen; Li, Chunlei; Li, Cheng; Chen, Jun

doi:10.2147/copd.s393323

Cited by 11 publications

(5 citation statements)

References 81 publications

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“…GLP-1 as an incretin hormone possesses anti-inflammatory and immune-modulatory functions, and its receptor agonists contribute to decreased blood glucose levels [ 28 ]. Available studies have suggested that GLP-1 and its based agents have therapeutic potential in lung injury and COPD [ 29 , 30 ]. Wei et al have shown that GLP-1-based pharmaceuticals presented reduced occurrence in most chronic lung diseases, except for interstitial lung disease [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

Su,

Zhang,

2024

BMC Pulm Med

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Background Previous research has emphasized the potential benefits of anti-diabetic medications in inhibiting the exacerbation of Chronic Obstructive Pulmonary Disease (COPD), yet the role of anti-diabetic drugs on COPD risk remains uncertain. Methods This study employed a Mendelian randomization (MR) approach to evaluate the causal association of genetic variations related to six classes of anti-diabetic drug targets with COPD. The primary outcome for COPD was obtained from the Global Biobank Meta-analysis Initiative (GBMI) consortium, encompassing a meta-analysis of 12 cohorts with 81,568 cases and 1,310,798 controls. Summary-level data for HbA1c was derived from the UK Biobank, involving 344,182 individuals. Positive control analysis was conducted for Type 2 Diabetes Mellitus (T2DM) to validate the choice of instrumental variables. The study applied Summary-data-based MR (SMR) and two-sample MR for effect estimation and further adopted colocalization analysis to verify evidence of genetic variations. Results SMR analysis revealed that elevated KCNJ11 gene expression levels in blood correlated with reduced COPD risk (OR = 0.87, 95% CI = 0.79–0.95; p = 0.002), whereas an increase in DPP4 expression corresponded with an increased COPD incidence (OR = 1.18, 95% CI = 1.03–1.35; p = 0.022). Additionally, the primary method within MR analysis demonstrated a positive correlation between PPARG-mediated HbA1c and both FEV1 (OR = 1.07, 95% CI = 1.02–1.13; P = 0.013) and FEV1/FVC (OR = 1.08, 95% CI = 1.01–1.14; P = 0.007), and a negative association between SLC5A2-mediated HbA1c and FEV1/FVC (OR = 0.86, 95% CI = 0.74–1.00; P = 0.045). No colocalization evidence with outcome phenotypes was detected (all PP.H4 < 0.7). Conclusion This study provides suggestive evidence for anti-diabetic medications' role in improving COPD and lung function. Further updated MR analyses are warranted in the future, following the acquisition of more extensive and comprehensive data, to validate our results.

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Section: Discussionmentioning

confidence: 99%

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

Su,

Zhang,

2024

BMC Pulm Med

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“…In addition, GLP-1RAs inhibit NLRP3 inflammasome both directly and indirectly. Shao et al ( Wang W. et al, 2023 ) found that GLP-1RAs mitigate liver damage caused by oxidative stress by promoting the mitophagy pathway and suppressing the NLRP3 inflammasome, an effect that can be eliminated by PINK1 siRNA.…”

Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Wang,

Ding,

Cheng

et al. 2024

Front. Pharmacol.

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Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients’ long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells’ synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

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“…GLP-1R reduces the inflammatory-induced response in the lungs, regulates oxidative stress and pulmonary function, and decreases excessive mucus production [47,48]. Furthermore, GLP-1R affects the mucosal membrane in the gastric tract by decreasing gastric secretions, which restrict gastric acid secretions and motility [49][50][51].…”

Section: Glucagon-like Peptide-1 Receptormentioning

confidence: 99%

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Ibrahim,

Arabi

et al. 2024

Cancer Metastasis Rev

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Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

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The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease

Cited by 11 publications

References 81 publications

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

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