Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 12 2 2022 03 09 Exendin-4 as a Versatile Therapeutic Agent for the Amelioration of Diabetic Changes 237 247 10.34172/apb.2022.025 EN Hadi Rajabi https://orcid.org/0000-0001-6086-591X Mahdi Ahmadi Somayeh Aslani Shirin Saberianpour Reza Rahbarghazi https://orcid.org/0000-0003-3864-9166 REVIEW 10.34172/apb.2022.025 2020 06 02 2021 01 29 Type 2 diabetes mellitus (T2DM) is a chronic metabolic abnormality leading to microvascular and macrovascular complications. Non-insulin Incretin mimic synthetic peptide exendin-4 was introduced as an anti-diabetic drug which helped diabetic patients with triggering insulin secretion; further researches have revealed an effective role of exendin-4 in treatment of T2DM related diseases. Exendin-4 is approximately similar to Glucagon-like peptide, thus it can bind to the glucagon-like peptide-1 receptor (GLP-1R) and activated different signaling pathways that are involved in various bioactivities such as apoptosis, insulin secretion and inactivation of microglial. In this review, we investigated the interesting role of exendin-4 in various kinds of T2DM related disorders through the activation of different signaling pathways.