Therapeutic effects of anti-diabetic drugs on traumatic brain injury

• Published in: Diabetes & metabolic syndrome clinical research & reviews 2024-02, Vol.18 (2), p.102949-102949, Article 102949
• Main Authors: Razavi, Seyed Mehrad, Arab, Zahra Najafi, Niknejad, Amirhossein, Hosseini, Yasamin, Fouladi, Abtin, Khales, Saba Darban, Shahali, Mostafa, Momtaz, Saeideh, Butler, Alexandra E., Sukhorukov, Vasily N., Jamialahmadi, Tannaz, Abdolghaffari, Amir Hossein, Sahebkar, Amirhossein
• Format: Article
• Language: English
• Subjects: Anti-diabetic drugs; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Humans; Inflammation; Inflammation - complications; Kelch-Like ECH-Associated Protein 1 - metabolism; Metformin; NF-E2-Related Factor 2 - metabolism; NF-E2-Related Factor 2 - therapeutic use; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Traumatic brain injury (TBI)
• ISSN: 1871-4021; 1878-0334
• DOI: 10.1016/j.dsx.2024.102949

In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/β-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted. •Traumatic brain injury (TBI) is a serious brain disease caused by trauma.•Recent studies suggest that oral anti-diabetic drugs could have beneficial effects in the management of TBI complications.•The protective effects of anti-diabetic drugs in TBI may involve downregulation of inflammatory and oxidative pathways.•Herein, the effects of anti-diabetic drugs on TBI complications as well as underlying mechanisms of action are reviewed.