The GLP-1 receptor in airway inflammation in asthma: a promising novel target?

Wu, Ashley Y; Peebles, R. Stokes

doi:10.1080/1744666x.2021.1971973

Cited by 12 publications

(9 citation statements)

References 33 publications

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“…The cumulative incidence curves in the GLP-1 receptor agonist versus sulfonylurea cohort diverged after eight months of use. The timing of this effect fits with the hypothesised mechanisms of GLP-1 receptor agonists on exacerbations of chronic obstructive pulmonary disease, which include local anti-inflammatory, smooth muscle relaxation, and structural modifications 44. On the other hand, the cumulative incidence curves in the SGLT-2 inhibitor versus sulfonylurea cohort diverged earlier.…”

Section: Discussionsupporting

confidence: 60%

“…The timing of this effect fits with the hypothesised mechanisms of GLP-1 receptor agonists on exacerbations of chronic obstructive pulmonary disease, which include local anti-inflammatory, smooth muscle relaxation, and structural modifications. 44 On the other hand, the cumulative incidence curves in the SGLT-2 inhibitor versus sulfonylurea cohort diverged earlier. Lastly, some secondary analyses, such as those stratifying on individual drugs, generated fewer exposed events and wide confidence intervals.…”

Section: Discussionmentioning

confidence: 99%

“…Several potential mechanisms may explain the decreased risk of chronic obstructive pulmonary disease exacerbation observed with GLP-1 receptor agonists. Firstly, GLP-1 receptor agonists have been shown to reduce local inflammation and airway hyperresponsiveness in murine models,4544 in isolated human airways,3 and among patients with type 2 diabetes and chronic obstructive pulmonary disease 45. In short term randomised controlled trials, GLP-1 receptor agonists have been shown to improve surrogate measures of lung function, such as forced vital capacity 67.…”

Section: Discussionmentioning

confidence: 99%

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Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study

Pradhan

Yin

et al. 2022

BMJ

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Objective To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes. Design Population based cohort study using an active comparator, new user design. Setting The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. Participants Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14 259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10 841 starting sulfonylureas. Main outcome measures Cox proportional hazards models with propensity score fine stratification weighting were fitted to estimate hazard ratios and 95% confidence intervals of severe exacerbation of chronic obstructive pulmonary disease (defined as hospital admission for chronic obstructive pulmonary disease), separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Whether these drugs were associated with a decreased risk of moderate exacerbation (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute chronic obstructive pulmonary disease exacerbation on the same day) was also assessed. Results Compared with sulfonylureas, GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94). DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 v . 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value. Finally, SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 v 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27). Conclusions In this population based study, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease and type 2 diabetes. DPP-4 inhibitors were not clearly associated with a decreased risk of chronic obstructive pulmonary disease exacerbations.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study

Pradhan

Yin

et al. 2022

BMJ

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“…Recently, He and collaborators reported that gut intraepithelial T cells regulate GLP-1 bioavailability by capturing GLP-1 on GLP-1Rs and impacting L cell numbers [ 81 ]. GLP-1R agonists can regulate OVA-induced airway inflammation and mucus secretion in mice [ 35 ], which are related to the inhibitory effect of GLP-1R signaling on Th2 inflammation [ 82 ]. Rapid secretion of GLP-1 occurs before the nutrients reach the ileum and colon, where large numbers of L cells are concentrated [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

The Interaction of Food Allergy and Diabetes: Food Allergy Effects on Diabetic Mice by Intestinal Barrier Destruction and Glucagon-like Peptide 1 Reduction in Jejunum

Yao

Jiang

et al. 2022

Foods

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The increase in food allergies and diabetes leads to the assumption that they are related. This study aimed to (1) verify the interaction between food allergy and diabetes and (2) explore the potential mechanisms by which food allergy promotes diabetes. Female BALB/c mice were grouped into a control group (CK), an ovalbumin-sensitized group (OVA), a diabetes group (STZ), and a diabetic allergic group (STZ + OVA) (Mice were modeled diabetes with STZ first, then were given OVA to model food allergies), and an allergic diabetic group (OVA + STZ) (Mice were modeled food allergies with OVA first, then were given STZ to model diabetes). The results showed that OVA + STZ mice exhibited a more serious Th2 humoral response, and they were more susceptible to diabetes. Furthermore, when the OVA + STZ mice were in the sensitized state, the intestinal barrier function was severely impaired, and mast cell activation was promoted. Moreover, we found that the effect of food allergy on diabetes is related to the inhibition of GLP-1 secretion and the up-regulation of the PI3K/Akt/mTOR/NF-κB P65 signaling pathway in the jejunum. Overall, our results suggest that food allergies have interactions with diabetes, which sheds new light on the importance of food allergies in diabetes.

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“…Glucagon‐like peptide‐1 (GLP‐1), an intestinal L‐cell‐synthesized peptide hormone, serves as a key player in regulating the insulin/glucagon balance 80 . Numerous studies have focused on the potential therapeutic application of GLP‐1 in ILC2‐mediated asthma 81,82 . Specifically, liraglutide, a GLP‐1 receptor (GLP‐1R) agonist that is utilized in the management of obesity and type 2 diabetes, 83 can hinder ILC2 activation in Alternaria ‐induced allergic lung inflammation by decreasing IL‐33 secretion produced by lung epithelial cells 84 .…”

Section: Peptide/protein Hormones In Ilc2‐mediated Allergic Lung Infl...mentioning

confidence: 99%

The role of hormones in ILC2‐driven allergic airway inflammation

Dai,

Gong,

Wang

et al. 2024

Scand J Immunol

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Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL‐5 and IL‐13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial‐derived alarmins, such as IL‐33, IL‐25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2‐driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.

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The GLP-1 receptor in airway inflammation in asthma: a promising novel target?

Cited by 12 publications

References 33 publications

Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study

Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study

The Interaction of Food Allergy and Diabetes: Food Allergy Effects on Diabetic Mice by Intestinal Barrier Destruction and Glucagon-like Peptide 1 Reduction in Jejunum

The role of hormones in ILC2‐driven allergic airway inflammation

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