Neuroprotective Effect of Sitagliptin beyond the Incretin Effect: A Narrative Review

Sitagliptin is a dipeptidyl peptidase-IV inhibitor approved for treating type 2 diabetes mellitus. It increases the active form of incretin Glucagon-like Peptide-1 (GLP-1). The GLP-1 peptide prevents damage to neurons due to its anti-inflammatory and anti-apoptotic activities. This article summarizes the studies assessing the neuroprotective properties of sitagliptin, especially through the GLP-1 pathway. The outcomes of experimental research indicate that sitagliptin has a decreasing effect on inflammation response. Sitagliptin decreases proinflammatory factors, such as Glial Fibrillary Acidic Protein (GFAP), Nuclear factor kappa B (NF-κB), Tumor Necrosis Factor-α (TNF- α), and Interleukin-6 (IL-6). It also decreases glutamate levels, the primary excitatory neurotransmitter. Furthermore, sitagliptin shows antioxidative and antiapoptotic effects. Lastly, sitagliptin may provide a novel agent for the management of neurological disease.