Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored.

This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity.

We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers.

In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001).

GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms.

The relationship between diabetes mellitus (DM) and asthma is complex and can impact disease trajectories.

To explore the bidirectional influences between the two conditions on clinical outcomes and disease control.

We systematically reviewed the literature on the relationship between DM and asthma, focusing on their impacts, mechanisms, and therapeutic implications. Various studies were assessed, which investigated the effect of glycemic control on asthma outcomes, lung function, and exacerbations. The study highlighted the role of specific diabetes medications in managing asthma.

The results showed that poor glycemic control in diabetes can exacerbate asthma, increase hospitalizations, and reduce lung function. Conversely, severe asthma, especially in obese individuals, can complicate diabetes management and make glycemic control more difficult. The diabetes-associated mechanisms, such as inflammation, microangiopathy, and oxidative stress, can exacerbate asthma and decrease lung function. Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations.

The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes. Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes, while asthma severity, especially in obese individuals, complicates diabetes control. However, the current research has limitations, and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.

Chronic respiratory disorders are the third leading cause of mortality globally. Consequently, there is a continuous pursuit of effective therapies beyond those currently available. The therapeutic potential of the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide/GLP-1 (GIP/GLP-1) receptor agonists extends beyond the regulation of glycemia, including glucometabolic, cardiovascular, and renal effects, rendering them viable candidates, due to their mechanisms of action, for the possible treatment of respiratory disorders. This manuscript aims to provide a comprehensive evaluation of the evidence on potential direct (cellular) and indirect (metabolic) actions of GLP-1 and GIP/GLP-1 receptor agonists within the pulmonary systems. In addition, it examines their efficacy in addressing prevalent respiratory disorders, specifically chronic obstructive pulmonary disease (COPD), asthma, pneumonia, obstructive sleep apnea, pulmonary hypertension, lung cancer, and lung transplantation. Finally, the manuscript seeks to identify potential avenues for further focused research in this field.

Difficult-to-treat and severe asthma are challenging clinical entities. In the face of suboptimal asthma control, the temptation for clinicians is to reflexively escalate asthma-directed therapy, including increasing exposure to corticosteroids and commencement of costly but potent biologic therapies. However, asthma control is objectively and subjectively assessed based on measurable parameters (such as exacerbations or variability in pulmonary physiology), symptoms and patient histories. Crucially, these features can be confounded by common untreated comorbidities, affecting clinicians' assessment of asthma treatment efficacy.

Asthma is a heterogenous disorder driven by inflammatory mechanisms that result in multiple phenotypes. Given the complex nature of this condition, metabolomics is being used to delineate the pathobiology of asthma. Metabolomics is the study of metabolites in biology, which includes biofluids, cells, and tissues. These metabolites have a vital role in a disease as they contribute to the pathogenesis of said condition. This review describes how macrometabolic and micrometabolic studies pertaining to these metabolites have contributed to our current understanding of asthma, as well as its many phenotypes. One of the main phenotypes this review will discuss in further detail is obesity as well as diabetes. Distinct roles of metabolites in endotyping asthma and their translation to potential therapy development for asthma is also discussed in this review.

There is substantial epidemiological and experimental evidence of an obesity-related asthma phenotype. Compared to children of healthy weight, children with obesity are at higher risk of asthma. Children with obesity who have asthma have greater severity and poorer control of their asthma symptoms, more frequent asthma exacerbations, and overall lower asthma-related quality of life than children with asthma who have a healthy weight. In this Review, we examine some of the latest evidence on the characteristics of this phenotype and its main underlying mechanisms, including genetics and genomics, changes in airway mechanics and lung function, sex hormone differences, alterations in immune responses, systemic and airway inflammation, metabolic dysregulation, and modifications in the microbiome. We also review current recommendations for the treatment of these children, including in the management of their asthma, and current evidence for weight loss interventions. We then discuss initial evidence for potential novel therapeutic approaches, such as dietary modifications and supplements, antidiabetic medications, and statins. Finally, we identify knowledge gaps and future directions to improve our understanding of asthma in children with obesity, and to improve outcomes in these susceptible children. We highlight important needs, such as designing paediatric-specific studies, implementing large multicentric trials with standardised interventions and outcomes, and including racial and ethnic groups along with other under-represented populations that are particularly affected by obesity and asthma.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved to treat type 2 diabetes mellitus. The anti-inflammatory and anti-obesity properties of GLP-1 RAs as well as their moderating effects on multiple pathobiological pathways in asthma pathogenesis may decrease asthma exacerbations, improve quality of life, and decrease premature death among patients with asthma and co-morbid diabetes or obesity. The aim of this literature review is to discuss evidence from basic science, human studies, and clinical trials to support the preferential use of GLP-1 RAs in asthma patients with co-occurring diabetes and obesity. The preliminary data on the effect of GLP-1 RAs on asthma in patients with diabetes are promising and merit further trials and research studies.