Background The glucose lowering glucagon-like peptide-1 receptor (GLP1R) agonists are currently used in the clinic for the treatment of type 2 diabetes mellitus (T2DM). Interestingly, recent meta-analyses demonstrate beneficial effects on cardiovascular (CV) outcomes. Preclinical studies suggest that this is rather regulated by inducing anti-inflammatory effects than improving dyslipidemia. However, the effects of GLP1R agonists on the immune system remain to be determined in humans. A population typically more prone to develop CV diseases and T2DM as compared to Europids are the South Asians. In this study, we aimed to investigate the effect of long-term treatment with the GLP1R agonist liraglutide on gene expression of markers of the immune system in blood in overweight T2DM patients from South Asian and European descent.

Methods Fasted blood samples were obtained before and after 26 weeks liraglutide treatment (1.8 mg/day SC), from overweight T2DM patients from South Asian (n=7; age 58 ± 7.9 years) and Europid (n=11; age 62 ± 3.7 years) descent. We measured mRNA expression of 144 immune genes in blood using a dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA) assay.

Results On baseline, expression levels of 11/144 genes were significantly different in South Asians compared to Europids. In South Asians only, liraglutide treatment modified expression of all these genes to similar expression as in Europids. In total, in South Asians but not in Europids, 51/144 genes were significantly changed after treatment. More specifically, several markers of pattern recognition receptors (TRL2, TLR3, TLR4, TLR5, TLR8, NOD1, NOD2) and T-cells (TBX21, CCR7, IL9, IL13, IL2RA, LAG3, FOXP3, TNFRSF18) were downregulated after treatment.

Conclusions South Asian patients with overweight and T2DM exhibit a different expression of several immune related genes compared to Europids. Long-term liraglutide treatment downregulates expression of several markers of pattern recognition receptors and T-cells in in South Asians only.