GLP-1 Receptor Agonists and Risk of Paralytic Ileus: A drug-target Mendelian Randomization Study
Year: 2024
Type: preprint
Study design: Observational Study
Abstract: Background Paralytic ileus (PI), a condition characterized by reduced bowel motor activity without physical obstruction, can be affected by complications from type 2 diabetes (T2D) and anti-diabetic medications. It is unclear of the causal associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with the risk of PI in the context of T2D management. Methods To investigate the causal relationship of GLP-1RAs with PI, we conducted a 2-sample mendelian randomization (MR) study based on summary statistics from genome-wide association studies (GWAS). Genetic variants in the GLP1R were identified as genetical proxies of GLP-1RAs by the glycemic control therapy, based on genetic associations with glycated hemoglobin (GWAS n=344,182) and T2D (n cases/controls =228,499/1,178,783). The effects of GLP-1RAs were estimated for PI risk (n cases/controls =517/182,423) using GWAS data from the FinnGen project. Results Based on MR analysis, GLP-1RAs are causally associated with a decreased risk of PI (OR per 1 mmol/mol decrease in glycated hemoglobin: 0.21; 95% confidence interval [CI]=0.06-0.69). The magnitude of these benefit exceeded those expected from improved glycemic control more generally. Conclusions Our study’s findings show that GLP-1RAs are causally associated with a lower risk for PI, which provides information to guide clinicians in the selection of appropriate therapies for individuals with T2D while mitigating the risk of developing PI. Investigating the underlying mechanisms that contribute to the lower PI risk associated with GLP-1RAs is essential for a deeper understanding of these associations.
Source: medRxiv
Institution: Case Western Reserve University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Combine computational prediction, network analysis and genetic screening in C elegans to uncover neurodegenerative causes in Alzheimer's Disease, Construct large-scale phenomes of disease and drugs and develop data-driven systems approaches to understand genetic links between Alzheimer's disease and Neuropsychiatric symptoms, Characterize multifaceted interactions between COVID-19 and alcohol use disorder based on real-time analysis of electronic health records of 62 million adult patients, An Integrated Reverse Engineering Approach Toward Rapid drug Re positioning for Alzheimer's Disease
OpenAlex ID: W4403552071