Traumatic brain injury (TBI) is becoming an increasing public health issue. With an annually estimated 1.7 million TBIs in the United States (U.S) and nearly 70 million worldwide, the injury, isolated or compounded with others, is a major cause of short- and long-term disability and mortality. This, along with no specific treatment, has made exploration of TBI
therapies a priority of the health system. Age and sex differences create a spectrum of vulnerability to TBI, with highest prevalence among younger and older populations. Increased public interest in the long-term effects and prevention of TBI have recently reached peaks, with media attention bringing heightened awareness to sport and war related
head injuries. Along with short-term issues, TBI can increase the likelihood for development of long-term
neurodegenerative disorders. A growing body of literature supports the use of
glucagon-like peptide-1 (GLP-1),
glucose-dependent insulinotropic peptide (GIP), and
glucagon (Gcg) receptor (R) agonists, along with unimolecular combinations of these
therapies, for their potent neurotrophic/neuroprotective activities across a variety of cellular and animal models of chronic
neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and acute
cerebrovascular disorders (
stroke). Mild or moderate TBI shares many of the hallmarks of these conditions; recent work provides evidence that use of these compounds is an effective strategy for its treatment. Safety and efficacy of many
incretin-based
therapies (
GLP-1 and GIP) have been demonstrated in humans for the treatment of
type 2 diabetes mellitus (T2DM), making these compounds ideal for rapid evaluation in clinical trials of mild and moderate TBI.