# Incretin Mimetics as Potential Therapeutics for Concussion and Traumatic Brain Injury: A Narrative Review

## TL;DR

This paper reviews how incretin mimetics, used for diabetes, might also help treat traumatic brain injuries and concussions by reducing inflammation and protecting brain tissue.

## Contribution

The paper highlights the novel potential of incretin-based compounds as neuroprotective agents for TBI, supported by preclinical and limited clinical evidence.

## Key findings

- Incretins show neurotrophic and neuroprotective effects in cellular and animal models of TBI.
- Incretin-based compounds are already safe and effective for diabetes, making them promising candidates for rapid clinical evaluation in TBI.
- Current TBI treatments are limited, and incretins could offer a novel therapeutic approach.

## Abstract

Traumatic brain injury (TBI) represents a significant health concern, with an estimated 70 million annual cases worldwide. Mild brain trauma (concussions) is the most common TBI (81%), followed by moderate (11%) and severe (8%). Cytokine release and neuroinflammation after TBI may cause blood–brain barrier and tissue damage, triggering unfavorable outcomes, including disabilities and mortality. Current TBI treatments, focused on preventing secondary injury, are limited and insufficient. Therefore, new therapeutic approaches are necessary. A growing body of recent literature supports the potential use of incretins: glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and glucagon receptor agonists, as potent neurotrophic/neuroprotective agents. Experiments performed in cellular and animal models, and a limited number of clinical studies, provide evidence that incretins might be a novel and effective treatment for TBI. Incretin-based compounds have already been shown to be safe and efficacious for the treatment of type 2 diabetes mellitus in humans. Therefore, incretins are ideal candidates for rapid evaluation in clinical trials of TBI and might become a novel therapeutic tool for a condition that has very few disease modifying treatments available. Well-designed human clinical trials are urgently needed to determine optimal dosing, timing, and patient selection for effective incretin use in concussion and TBI.