The effects of GLP-1RA on inflammatory skin diseases: A comprehensive review

Abstract

Glucagon-like peptide 1 receptor agonists (GLP-1RA) are commonly used as treatment for type 2 diabetes mellitus and obesity. GLP-1RA have been found to be valuable therapeutic approaches not only for glucose control, but also for weight loss and cardiovascular risk reduction. It has also been established that GLP-1RA have immunological and anti-inflammatory effects. The aim of this article was to comprehensively review the literature and to collect, analyse and quantitatively resynthesize evidence on the possible effects of GLP-1RA on inflammatory skin diseases. Through body weight reduction and subsequent systemic inflammation reduction, but mainly through their direct interaction with signalling pathways of inflammation and immune cells, GLP-1RA can improve psoriasis and hidradenitis suppurativa (HS). Clinical data of the positive effects of GLP-1RA in patients with psoriasis and HS are presented. Moreover, the immune cells and inflammatory pathways affected by GLP-1RA are discussed.

FIGURE 1

Actions of GLP‐1RA on glucose metabolism. The direct and indirect metabolic effects of the GLP‐RA on various organs are presented.

FIGURE 2

The effect of GLP‐1RA on iNKT cells. INKT cells upon stimulation are able to produce inflammatory cytokines, which are involved in the pathogenesis of psoriasis. The activation of the iNKT cells is possible when a lipid antigen is being presented by CD1d to the iNKT cell. The iNKT cell express GLP‐1R. Stimulation of the receptor inhibits NF‐kB, and thus, the secretion of proinflammatory cytokines.

FIGURE 3

Suggested mechanisms responsible for improvement in psoriasis severity in patients receiving GLP1‐RA. GLP‐1RA: glucagon‐like peptide 1 receptor agonist, iNKT cells: invariant natural killer T cells, NF‐kB: nuclear factor kappa B, TNF‐a: tumour necrosis factor‐a, PI3K: phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, SDF‐1: stromal cell‐derived factor 1.