Preclinical study suggests neuroprotective potential of liraglutide and twincretin in post-mTBI mice

Bader et al. investigated the treatment potential of two drugs, liraglutide and twincretin, in post-concussion mice. Previous research suggests that drug analogs of the hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) can have neuroprotective effects in animals. Liraglutide is a GLP-1 analog; twincretin is an analog to both GLP-1 and GIP. 

Published in Frontiers in Cell and Developmental Biology, the study consisted of 115 mice (6-8 weeks old) randomly assigned to one of four groups: non-mTBI, mTBI, mTBI+liraglutide, and mTBI+twincretin. Mice received daily drug (or saline) injections for a week.

Three days post-impact, mice in the mTBI group had elevated markers for neurodegeneration in several brain regions. Mice treated with liraglutide and twincretin had less-elevated microglial activity, suggesting the drugs may minimize neuroinflammation after mTBI. Further, “Both drugs ameliorated mTBI-induced cognitive impairments” and neurodegeneration.

Relative to mTBI mice, those treated with either medication had less impaired visual and spatial memory one week and one month post-impact. Mice treated with twincretin showed greater improvement in visual memory than liraglutide mice.

mTBI significantly decreased the activity of the neuroprotective protein PKA within the hippocampus and cortex (measured by phosphorylation levels) but both drug treatments mitigated this reduction. 

The study offers promising preliminary results, but further research is needed to clarify the signaling pathways that liraglutide and twincretin utilize in the brain. Also, whereas liraglutide is an FDA-approved treatment for type 2 diabetes, twincretin remains less understood.