Enterostatin is a class of factors secreted by the intestine that promotes glucose-stimulated insulin secretion. The English name incretin is a combination of intestine, secretion and insulin, and was first described by Bayliss and Starling in 1902 as a factor derived from intestinal mucus that promotes pancreatic secretion. DDP-4 is an enzyme that can inactivate GLP-1. The effect of enteroglucagon on insulin secretion in humans was observed in eight healthy volunteers who were given 50g/400ml of glucose orally or 180 minutes of intravenous glucose infusion after overnight fasting. The results showed similar changes in intravenous plasma glucose, but the insulin response was significantly enhanced in the oral glucose group compared to the intravenous glucose infusion, suggesting an effect of enteroglucagon on insulin secretion. This insulin response after oral glucose loading was stronger than that induced by intravenous glucose loading at similar glucose profiles. This phenomenon is known as the “entero-insulin effect” because it is caused by the secretion of entero-insulin hormone following oral glucose administration rather than intravenous glucose. A clinical study showed that the entero-insulin effect was reduced in patients with type 2 diabetes compared to healthy controls with normal metabolism. The glucose profiles produced by the oral glucose load group and the intravenous glucose load group were essentially similar, and although insulin levels after oral glucose load were higher than intravenous glucose load in both groups, the intestinal proinsulin effect was still significantly diminished in diabetic patients. Currently, the main enterostatin found in humans are Glucagon-Like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP). Both polypeptides are highly homologous to the amino acid sequence of glucagon. GLP-1 in healthy human is secreted mainly by L cells in ileum and colon, and its basal concentration in human body is about 5-10 pmol/L, and the concentration can be increased 2-3 times after meal. In patients with type 2 diabetes, serum GLP-1 levels are significantly reduced, but its biological activity is not impaired. Immunohistochemical staining shows that GLP-1 production is quickly followed by inactivation by DPP-4. There are currently two main R&D strategies based on enteroglucagon: the first is the development of drugs that mimic the action of GLP-1, i.e. GLP-1 analogues (which are not degraded by DPP-4), and the second strategy is the development of DPP-4 inhibitors, i.e. drugs that prolong the activity of endogenous GLP-1. DPP-4 inhibitors increase the level of active enteroglucagon, thereby increasing and prolonging its effect. The following is an example of the mechanism of action of DPP-4 inhibitors using selegiline. Eating stimulates the rapid release of enteric islet hormone from the gastrointestinal tract: GLP-1 is secreted by L cells located mainly in the distal intestine, and GIP is secreted by K cells in the proximal intestine. These enteric islet hormones exert numerous beneficial effects, including a glucose-dependent pattern of stimulating the insulin-secreting response of pancreatic β-cells, reducing the increase in blood glucose levels caused by glucagon production by pancreatic α-cells, increasing insulin levels to enhance glucose uptake by peripheral tissues, increasing the insulin response and reducing hepatic glucose production by decreasing glucagon. Enteroglucagon is rapidly inactivated by dipeptidyl peptidase 4 (DPP-4), and the effect of enteroglucagon is reduced in patients with type 2 diabetes, resulting in lower GLP-1 levels and reduced GIP effects. By inhibiting DPP-4 selegiline effectively prevents the degradation of entero-insulin and increases the level of active entero-insulin, which in turn enhances the body’s own ability to control blood glucose. Selegiline increases the concentration of active entero-insulin hormones, thereby increasing and prolonging the effects of these hormones and ultimately lowering fasting and postprandial blood glucose. The main drugs that have entered clinical studies are Sitagliptin, Vildagliptin, Saxagliptin, and Alogliptin. Clinical studies have shown that monotherapy with each of these drugs is effective in reducing glycated hemoglobin. The combination of these drugs with metformin was also able to significantly reduce glycated hemoglobin levels compared to metformin alone. Research studies evaluating the cardiovascular safety of Incretin-based therapeutic agents include TECOS, EXAMINE, SAVOR:, CAROLINA, EXSCEL, LEADER, and ELIXA. To date, the U.S. FDA has approved DPP-4 inhibitors: Sitagliptin, Vildagliptin, Saxagliptin, and Linagliptin. Overall, no clinically significant drug interactions were identified in the drug interaction studies. In vivo studies have shown that selegliptin does not inhibit CYP isoenzymes CYP3A4, 2C8 or 2C9; in vitro studies have shown that selegliptin does not inhibit CYP2D6, 1A2, 2C19 or 2B6 or induce CYP3A4. However, saxagliptin, which is metabolized by hepatic CYP3A4/5, when used with CYP3A4/5 inhibitors such as ketoconazole, requires reduce the 5 mg/d dose by half. In conclusion, the current study shows that DPP-4 inhibitor therapy produces clinically meaningful and statistically significant decreases in HbA1c, PPG and FPG, and achieves comprehensive glycemic control; has a good safety and tolerability profile with a low incidence of hypoglycemia risk and no or minor weight changes; and a retrospective analysis of a large phase 2b/3 population showed no unsafe signals of cardiovascular events. 4 inhibitors offer a treatment option with a good benefit/risk ratio for patients with type 2 diabetes who do not meet glycemic targets. Large-scale, prolonged clinical studies evaluating cardiovascular safety will provide us with more useful information.