PrefaceSaxagliptin is a potent dipeptidyl peptidase-4 (DPP-4) inhibitor that regulates blood glucose by selectively inhibiting DPP-4, which can elevate the levels of endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin-releasing polypeptide (GIP). GLP-1 is secreted in the intestine immediately after a meal, which in turn stimulates the pancreas to produce glucose-dependent insulin secretion, while inhibiting glucagon secretion and delaying gastric emptying. Under physiological conditions, DPP-4 rapidly degrades GLP-1 and GIP, rendering them inactive, while administration of DPP-4 inhibitors can increase endogenous GLP-1 levels 3-4-fold, effectively lowering HbA1c and postprandial glucose without affecting body weight and without significant risk of hypoglycemia. This year, the results of several clinical studies on saxagliptin have been published, consistently confirming its effects on lowering HbA1c, fasting glucose (FPG), postprandial glucose (PPG) levels and its good tolerability and safety. A few key results are briefly presented for your reference. Saxagliptin Monotherapy in Patients with Initial Type 2 Diabetes This is a clinical phase III, multicenter, parallel, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of initial treatment with saxagliptin monotherapy in patients with type 2 diabetes aged 18-77 years, whose blood glucose levels were not controlled by diet and exercise, and who were not yet on medication. Patients with baseline HbA1c levels ≥7% and ≤10% were enrolled in the main treatment cohort (MTC[l1]) and treated with saxagliptin 2.5 mg, 5 mg, 10 mg, or placebo orally once daily for 6 months. patients with HbA1c levels >10% and ≤12% were enrolled in the open-label cohort (OLC). label cohort (OLC), treated with saxagliptin 10 mg orally once daily for 24 weeks. The results showed that in the MTC group, saxagliptin significantly reduced corrected mean HbA1c levels from baseline (Figure 1), corrected mean FPG (-15, -9, -17 mg/dl versus +6 mg/dl in the placebo group) and postprandial glucose area under the curve (PPG-AUC) (-6868/-6896/-8084 mg.min/L versus -647 mg.min/L) in all 3 groups. Each glucose index was also significantly lower in the OLC group compared to baseline. All treatment groups had similar rates of adverse events to the placebo group, with no symptomatic (finger glucose ≤50 mg/dl) hypoglycemic events identified. Saxagliptin treatment also did not result in weight gain. Thus, saxagliptin monotherapy once daily had significant glycemic control with good safety and tolerability in primary care patients with either 7% ≤ HbA1c ≤ 10% or 10% ≤ HbA1c ≤ 12%. Addition of saxagliptin to type 2 diabetes in patients with poorly controlled metformin monotherapy Metformin is a first-line oral hypoglycemic agent recommended by several type 2 diabetes treatment guidelines that should be used in conjunction with lifestyle interventions. However, as the disease progresses, metformin monotherapy is often not sufficient to bring patients to glycemic targets, and many patients require a combination of oral hypoglycemic agents. When selecting additional drugs, try to use drugs that complement each other to counteract the complex pathophysiological pathogenesis of diabetes. Metformin regulates blood glucose by reducing hepatic glucose synthesis and improving insulin sensitivity; saxagliptin improves the postprandial β-cell response to glucose by inhibiting DPP-4, delaying entero-insulin inactivation, promoting glucose-mediated insulin release and reducing postprandial glucagon release. The combination of the two drugs has better glucose-lowering efficacy and has the potential to improve β-cell function and increase glycemic compliance. Professor DeFronzo et al. of San Antonio Health Sciences Center, San Antonio, Texas, USA, looked at the efficacy of adding saxagliptin 2.5, 5, and 10 mg once daily for 24 weeks in patients with uncontrolled glycemia on metformin monotherapy. The results showed that the HbA1c levels decreased by 0.59%, 0.69% and 0.58% in the three dose groups treated with saxagliptin, respectively, compared with an increase of 0.13% in patients treated with placebo, and the levels of FPG and PPG-AUC decreased significantly more than in the placebo group. The percentage of HbA1c compliance was significantly higher in patients treated with the addition of saxagliptin, both more than twice as high as in the placebo group (Table 1). All groups were well tolerated, and the incidence of hypoglycemia and weight changes were similar to those in the placebo group. In the study by Jadzinsky et al, 1306 patients with primary type 2 diabetes were enrolled and compared saxagliptin 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo or metformin 500 mg + placebo for 24 weeks. Of these, the dose of metformin could be adjusted upward to 2000 mg/d over 5 weeks. The results of the study showed that at week 24, the 2 combination treatment groups significantly reduced HbA1c, FPG and PPG-AUC in patients compared to the two monotherapy groups, with significant differences in outcomes. Patients in the saxagliptin 5 mg or 10 mg combined with metformin groups achieved the HbA1c<7% goal in 60.3% and 59.7% of patients, respectively. The incidence of adverse events was similar in all groups, with few hypoglycemic events. Subgroup analysis based on baseline HbA1c levels showed a more significant reduction in HbA1c levels after treatment in all treatment groups with higher baseline HbA1c levels (Figure 2). Figure 2 The reduction in HbA1c levels after treatment was more significant in those with higher baseline HbA1c levels saxagliptin + sulfonylurea in patients with type 2 diabetes mellitus with poor glycemic control sulfonylurea binds to sulfonylurea receptor 1 in β-cells ultimately stimulating insulin secretion. Studies have shown that sulfonylureas significantly improve blood glucose, but the shortcomings are their potential beta-cell toxicity, weight gain and increased risk of hypoglycemia. In contrast, smaller doses of sulfonylureas in combination with DPP-4 inhibitors can improve blood glucose early in the disease while reducing sulfonylurea dose-related adverse events. In one study, patients with poor glycemic control for ≥2 months on a lower-than-maximal therapeutic dose of sulfonylurea were randomized to saxagliptin 2.5 + glibenclamide 7.5 mg, 5 mg + glibenclamide 7.5 mg, and glibenclamide 10 mg single-dose dosing. At week 24, 92% of patients in the glibenclamide monotherapy group were dosed up to 15 mg. The study showed that the combination of saxagliptin 2.5 and 5 mg + glibenclamide 7.5 mg, respectively, significantly reduced HbA1c (-0.54%, -0.64%, +0.08%), FPG (-7, -10, +1 mg/dl) and PPG-AUC (- 4296, -5000, +1196 mg.min/dl). 22.4%, 22.8% and 9.1% of patients in the three groups met the standard, respectively. The incidence of adverse events was similar in all groups, and there was no significant difference in reported hypoglycemic events. Glycemic improvement was seen early in the combination treatment group, with a significant difference in HbA1c by week 4 (Figure 3), and was maintained throughout the treatment period. The study also showed that the AUC of postprandial insulin and C-peptide were more elevated and the AUC of postprandial glucagon was more reduced in the saxagliptin-treated group than in the glibenclamide monotherapy dosing group at week 24, which may be explained by the fact that saxagliptin enhanced the maximal proinsulin-releasing effect of sulfonylureas by elevating endogenous GLP-1 and GIP levels, promoting insulin synthesis and release, and improving beta-cell function This further supports the therapeutic strategy of combining saxagliptin when smaller doses of sulfonylureas are not sufficient for glycemic control. Figure 3 Summary of changes in HbA1c in each group during treatment In conclusion, saxagliptin monotherapy can effectively control blood glucose, and combination therapy with metformin or sulfonylurea can control blood glucose earlier and more effectively and improve patients' blood glucose attainment rate, while being safe to use and well tolerated. The HbA1c-lowering effect of saxagliptin is consistent across age, gender, race, BMI, geographic distribution, and duration of diabetes and is indicated for most patients with type 2 diabetes.