Pharmacological effects of vildagliptin is a selective dipeptide-peptidase-4 (DPP-4) inhibitor. It can quickly inhibit the activity of DPP-4 after administration, making the fasting and postprandial internal The levels of the source of glucagon GLP-1 (glucagon polypeptide-1) and GIP (glucose-dependent insulinotropic polypeptide) increase, thereby increasing the sensitivity of β-cells to glucose and promoting the secretion of glucose-dependent insulin. By increasing endogenous GLP-1 levels, vildagliptin can also increase the sensitivity of α cells to glucose, making glucose levels more consistent with glucagon secretion. During periods of hyperglycemia, vildagliptin lowers blood glucose by elevating incretin levels and increasing the insulin/glucagon ratio, resulting in decreased fasting and postprandial hepatic glucose production. Elevated GLP-1 levels are known to cause delayed gastrointestinal emptying, but this phenomenon did not occur after vildagliptin administration. Toxicological studies General toxicology: Cardiac conduction delay was observed in dogs after administration, and the no-effects dose was 15 mg/kg (calculated based on Cmax, which is the human exposure level when the dose is 100 mg (the same below) 7 times). An increase in alveolar macrophages was seen in rats and mice after administration. The non-responsive doses of the drug were 25 mg/kg (5 times the human exposure level based on AUC calculation) and 750 mg/kg (142 times) respectively. Gastrointestinal symptoms were seen in dogs after administration, especially soft stools, mucus, and diarrhea. Blood in the stool was found in the high-dose group. Unable to establish non-responsive dose of drug. In a 13-week toxicity study in cynomolgus monkeys, skin lesions were seen when vildagliptin was administered at doses ≥5 mg/kg/day, typically on the extremities (hands, feet, ears, and tail). Only reversible blisters were seen at a dose of 5 mg/kg/day (approximately equivalent to human exposure levels), and no abnormalities were found on histopathological examination. At a dose of ≥20 mg/kg/day (approximately 3 times the human exposure level), skin peeling, skin desquamation, scabs and tail ulcers, as well as corresponding histopathological changes, can be seen. Tail necrosis was seen at doses ≥80 mg/kg/day. During the 4-week recovery period, the skin lesions of animals in the 160 mg/kg/day group failed to recover. Genotoxicity: Routine in vitro and in vivo genotoxicity tests of vildagliptin were negative. Reproductive toxicity: In the fertility and early embryonic development toxicity test in rats, no effects on the fertility, reproductive behavior and early embryonic development of rats were found. In the embryo-fetal developmental toxicity test in rats and rabbits, fetal rib deformities were seen in rats after administration, accompanied by weight loss in the parent animals. The non-responsive dose was 75 mg/kg (10 times the human exposure level); in rabbits only Fetal weight loss and skeletal deformities suggestive of developmental delay were observed in cases of severe maternal toxicity at a no-response dose of 50 mg/kg (9 times the human exposure level). In the perinatal toxicity test in rats, maternal animal toxicity, transient weight loss, and decreased spontaneous activity in F1 generation animals were seen when the dose of vildagliptin was ≥150 mg/kg. Carcinogenicity: In a 2-year carcinogenicity test in mice, mice were orally administered vildagliptin at doses as high as 1,000 mg/kg (approximately 240 times the human exposure level). Increased incidences of breast cancer and angiosarcoma were seen at doses of 500 mg/kg (59 times the human exposure level) and 100 mg/kg (16 times the human exposure level), respectively. In a 2-year carcinogenicity test in rats, no increase in tumor incidence was seen when vildagliptin was administered orally at doses up to 900 mg/kg (approximately 200 times the human exposure level).