Tu138 - Impact of Liraglutide Treatment on Gene Expression in Peripheral T-cell Populations from Adults with Recently Diagnosed Type 1 Diabetes

Philippe Pagni – Novo Nordisk Research Center, Seattle Inc.; Hadas Lewinsky – Immunai Inc.; Priyanka Vijay – Immunai Inc.; Sara Murray – Novo Nordisk Research Center, Seattle Inc.; Alisa Greenberg – Immunai Inc.; Marisa Mariani – Immunai Inc.; Ramneek Gupta – Novo Nordisk Research Center, Oxford; Alena Jiraskova – Immunai Inc.; Iveta Mrizova – Immunai Inc.; Per Greisen – Novo Nordisk Research Center, Seattle Inc.; Chirag Sachar – Immunai Inc.; Johhna Wesley – Novo Nordisk Research Center, Seattle Inc.

Abstract Text: Type 1 diabetes is an autoimmune disease characterized by attack from immune cells infiltrating the pancreas and loss of functional beta-cell mass, requiring exogenous insulin treatment. Novo Nordisk has conducted a randomized, double-blind, placebo-controlled, phase 2 trial assessing whether the combination of GLP-1R agonist liraglutide and anti-IL-21 antibody could preserve beta-cell function. A collaboration with Immunai was established, leveraging a single cell multiomic approach to assay mRNA, protein, and TCR sequences with the 10x genomics platform, using select PBMC samples from the placebo (n=13) and liraglutide (n=11) arms of this trial, at baseline, (WK0) and end of treatment (WK54).
Immunai employed proprietary computational techniques to process sequence data, integrate sample and clinical metadata, annotate cell types, and compare cell type abundances and differential gene and pathway expression between WK0 and WK54 samples in the liraglutide and placebo arms. Downstream analysis focused on genes and pathways that changed from WK0 to WK54 in the liraglutide arm but did not show statistically significant changes from WK0 to WK54 in the placebo arm.
Compared to WK0, liraglutide-treated patients at WK54 have indicated decreased proliferation, cytotoxicity, and other markers of effector functions in NK and CD8+ T cells while indicating increased proliferation and suppressive function in Tregs. Of note, public human data repository analyses further substantiated a novel role for GLP-1R in Treg function, supporting the notion that GLP-1R might play a role in Tregs involved in autoimmunity and thereby guiding future clinical trials assessing GLP-1R agonists in type 1 diabetes.