Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases

Apr 2, 2025Journal of autoimmunity

Glucagon-like peptide-1 receptor activators as possible treatments that change autoimmune diseases

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

A total of 22 significant genetic variations were identified as proxies for exposure to GLP-1R agonists.

GLP-1R agonists are significantly associated with reduced odds of obesity (OR = 0.826) and type 2 diabetes mellitus (T2DM) (OR = 0.886).
Increased expression of the GLP-1R gene may have a protective effect against type 1 diabetes mellitus, hypothyroidism, primary biliary cholangitis, and rheumatoid arthritis.
Conversely, higher levels of GLP-1R agonists may be linked to an increased risk of Graves' disease, ulcerative colitis, and psoriasis.
The findings align with meta-analysis results, suggesting a complex relationship between GLP-1R agonists and autoimmune diseases.

AI simplified

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging with therapeutic agents for the treatment of two of the most prevalent metabolic disorders: diabetes and obesity. However, the causal relationship between GLP-1R agonists and autoimmune diseases is still unclear.

METHODS: The available cis-eQTLs for drug target genes (GLP-1Rs) were used as proxies for exposure to GLP-1R agonists. Obesity and type 2 diabetes mellitus (T2DM) were used as positive controls to ensure the reliability of the genetic instrument. Mendelian randomization (MR) was performed to reveal the causal association of genetic proxy GLP-1R agonists with 18 autoimmune diseases from the IEU OpenGwas database and FinnGen database. Finally, the results of the two databases were analyzed via meta-analysis.

RESULTS: A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instruments. Positive control analysis revealed that GLP-1R agonists were significantly associated with obesity (OR = 0.826, p = 0.021) and T2DM (OR = 0.886, p < 0.001), which is consistent with the meta-analysis. MR analysis revealed that increased expression of the GLP-1R gene has a significant protective effect on type 1 diabetes mellitus (T1DM), hypothyroidism, primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the MR analysis suggested that increased expression of GLP-1R agonists may increase the risk of Graves' disease (GD), ulcerative colitis (UC) and psoriasis. Our findings were consistent with those of the meta-analysis.

CONCLUSIONS: This study provides new insights into potential adjuvant treatments for autoimmune diseases from the perspective of genetic variation and provides evidence for the safety of GLP-1R agonists.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief