Effects of Sitagliptin and Metformin on Scopolamine-Induced Learning and Memory Impairment in Diabetic and Non-diabetic Mice

Background: Alzheimer’s disease (AD) is a neurodegenerative condition characterized by a gradual onset and progressive deterioration. Recent studies have demonstrated that certain antihyperglycemic drugs can slow down the progression of AD. Objectives: This study aimed to investigate the effects of sitagliptin (SG) and metformin (MTF) on scopolamine (SCP)-induced learning and memory impairment in both diabetic and non-diabetic mice. Methods: This experimental study was conducted with two subgroups of mice, one diabetic and one non-diabetic. Over a 14-day period, the animals received different doses of SG and MTF in addition to a combination of these two drugs. On the 14th day, SCP was administered, followed by a memory impairment test (passive avoidance learning) conducted 45 minutes later. Subsequently, the animals were sacrificed, and brain samples were collected to measure oxidative stress biomarkers, including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Results: The obtained findings revealed that intraperitoneal injection of SCP impaired learning and memory function and caused brain oxidative damage in both diabetic and healthy mice. In healthy mice, the administration of high doses of MTF (500 mg/kg) and SG (20 mg/kg), in addition to the combination of these two drugs, significantly reduced memory impairment and oxidative stress. However, in the diabetic groups, only MTF and the combination of MTF with SG could reduce memory impairment and oxidative stress. Conclusions: The authors concluded that these antidiabetic drugs ameliorated oxidative stress by increasing antioxidant capacity and improved scopolamine-induced memory impairment. Furthermore, the combination of these two drugs yielded more favorable results.