Advancing cardiovascular outcomes with dapagliflozin and sacubitril in post-acute myocardial infarction heart failure and type 2 diabetes mellitus

Coronary heart disease and type 2 diabetes mellitus(T2DM)often co-occur,presenting substantial health risks,particularly following acute myocardial infarction(AMI).While percutaneous coronary intervention(PCI)is a prevalent treatment,complications such as microvascular dysfunction may lead to heart failure,necessitating additional therapies.This editorial examines the emerging roles of sacubitril/valsartan and sodium-glucose co-transporter 2 inhibitors in managing post-PCI.Recent research investigates the combined effects of dapag-liflozin and telmisartan on myocardial microperfusion in post-AMI heart failure patients with T2DM.The findings suggest that this combination enhances myo-cardial microcirculation,improves cardiac function,and achieves better glycemic control,with a reduced incidence of major adverse cardiovascular events.Despite ongoing challenges,the integration of dapagliflozin and sacubitril/valsartan re-presents a significant advancement in post-AMI care.Further investigation in larger cohorts and more diverse patient populations is required to confirm its long-term clinical outcomes.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population.AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites.METHODS The patients studied were divided into two groups:100 patients in the control group received insulin,while 200 patients received dapagliflozin.These patients were classified as Child A,B,or C based on the Child–Pugh classification.Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin,respectively.RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin.In addition,dapagliflozin treatment substantially reduced weight,body mass index,and fasting blood glucose compared to the insulin group during follow-up.However,there were no significant differences in hemoglobin A1c,liver function,or laboratory investigations between both groups during the follow-up period.The incidence of hypoglycemia,hepatic encephalopathy,variceal bleeding,and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group.In contrast,the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness.In addition,the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group.CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites.This resulted in an improvement of ascites,as well as a decrease in diuretic dose and Child–Pugh score.

Clinical efficacy of dapagliflozin in the treatment of type 2 diabetes mellitus with heart failure with mildly reduced ejection fraction

Objective:To observe the clinical efficacy of dapagliflozin in the treatment of type 2 diabetes mellitus(T2DM)complicated with heart failure with mildly reduced ejection fraction(HFmrEF,40%≤LVEF<50%).Methods:A total of 84 patients with T2DM complicated with HFmrEF hospitalized in our hospital from October 2019 to October 2021 were selected,and random number table method was used to divide into the control group and the study group each 42 cases.Both groups used basal hypoglycemic and standardized anti-heart failure therapy,and the study group was treated with dapagliflozin simultaneously.Nine months later,the following indexes were compared between the two groups before and after treatment:the cardiac function indicators:N-terminal pro brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF);exercise endurance:6-minute walk distance(6MWD),NYHA cardiac function class,the score of the Minnesota living with heart failure questionnaire(MLHFQ)and the incidence of major adverse cardiovascular events(MACE).Results:Nine months later,the two groups showed decreased NT-proBNP level,increased LVEF,prolonged 6MWD,improved NYHA cardiac function grade,decreased MLHFQ score,and statistically significant differences within both groups compared with before treatment(P<0.05),after treatment significant differences were displayed between the two groups(P<0.05).Less patients had MACE events and adverse drug reactions in the study group compared with the control group.Conclusion:Dapagliflozin in the treatment of T2DM patients with HFmrEF can improve cardiac function indicators,improve exercise endurance,improve NYHA cardiac function class,improve patient's quality of life,and reduce the incidence of MACE events,with no obvious side effects.

Cost Utility Analysis of Dapagliflozin in Egyptian Patients with CKD from the Payer Perspective

Background: Chronic kidney disease is a serious public health issue in Egypt. An estimated 13% of individuals in Egypt are expected to have CKD, with a higher prevalence among older adults and in rural regions. The primary goal of the study was to compare the cost-utility of the standard of care alone against add-on medication, dapagliflozin, as a preventative measure against complications of CKD in cases with or without diabetes mellitus. Methods: A lifetime Markov state transition model with a 3-month cycle was employed based on the clinical evidence from the DAPA-CKD clinical trial. The model was to provide estimates of the long-term economic and health impact of managing CKD patients. Cost-effectiveness is assessed regarding the cost per quality-adjusted life year (QALY) gained. This economic evaluation study used a payer perspective. Moreover, the study evaluated the impact on the budget due to the undertaking of dapagliflozin. One-way deterministic sensitivity analyses, as well as a probabilistic sensitivity analysis, were employed. Results: During a lifetime horizon, the difference in cost between dapagliflozin and SOC was EGP -65,212 (USD 2126.89). The difference in QALY between dapagliflozin and SOC was 4.3. In CKD patients, adding dapagliflozin to ramipril generates better QALYs and lower costs than ramipril alone. Dapagliflozin improved the outcomes and generated cost savings. A deterministic one was sensitivity analysis revealed that the model is robust to changes in all variables included. Probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations showed that in about 82.64% of trials, dapagliflozin is cost-saving. The undertaking of dapagliflozin by any percent will have a positive impact on the budget. Conclusion: During the lifetime horizon, dapagliflozin is cost-saving;it benefits the quality of life and the total cost. The addition of dapagliflozin to SOC has a saving effect of 11.9% of the budget.

SGLT2抑制剂Dapagliflozin的全合成

以5-溴-2-氯苯甲酸和D-葡萄糖酸內酯为起始原料,完成了SGLT2抑制剂Dapagliflozin的全合成,总收率34.5%,其结构经NMR表征。

Dapagliflozin-糖尿病治疗的模式转变

Dapagliflozin在治疗2型糖尿病的临床前期和临床期研究表明,钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂增加肾糖排泄,可以降低血糖以及减轻体质量。大型试验论证了Dapagliflozin可能产生良好的效果而不出现重大不良反应,说明其具有安全性和有效性。因此,这类药物具有超过目前使用的许多降糖药的优势。现就SGLT2在糖代谢方面的作用和目前Dapagliflozin在治疗糖尿病中的应用进行综述。

Functional annotation and enrichment analysis of differentially expressed serum proteins in patients with type 2 diabetes after dapagliflozin

BACKGROUND Only 50% of patients with type 2 diabetes mellitus(T2DM) can control their blood glucose levels. Dapagliflozin is a selective inhibitor of sodium-glucose cotransporter 2(SGLT-2) that improves the insulin sensitivity of the liver and peripheral tissues. Many studies confirmed that SGLT2 inhibitors reduce blood glucose and have multiple beneficial effects such as weight loss, lipid regulation, and kidney protection. Nevertheless, the mechanisms of the renal and cardiovascular protective effects of dapagliflozin from the perspective of differentially expressed proteins in the serum of T2DM patients have not been intensively explored so far.AIM To identify differentially expressed proteins associated with dapagliflozin treatment in patients with T2DM.METHODS Twenty T2DM patients [hemoglobin A1c(HbA1c) 7.0%-10.0%] were enrolled at The Affiliated Hospital of Inner Mongolia Medical University between January 1, 2017 and December 1, 2018. They received dapagliflozin(10 mg/d) for 3 mo, and the HbA1c < 7.0% target was achieved. The changes in clinical indexes were compared before and after treatments. Label-free quantitative proteomics was used to identify differentially expressed proteins using the serum samples of five patients. The identified differentially expressed proteins were analyzed using various bioinformatics tools.RESULTS Dapagliflozin significantly improved the clinical manifestation of the patients. There were 18 downregulated proteins and one upregulated protein in the serum samples of patients after dapagliflozin administration. Bioinformatics analyses, including subcellular localization, Eu Karyotic Orthologous Groups, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes annotations, were used to profile the biological characteristics of the 19 differentially expressed proteins. Based on the literature and function enrichment analysis, two downregulated proteins, myeloperoxidase(MPO) and alpha Ⅱ B integrin(ITGA2B), and one upregulated protein, podocalyxin(PCX), were selected for enzyme linked immunosorbent assay validation. These validated differentially expressed proteins had multiple correlations with clinical indexes, including Hb Ac1 and fasting C-peptide.CONCLUSION Dapagliflozin has hypoglycemic effects and regulates the serum expressions of MPO, ITGA2B, and PCX, possibly contributing to the effects of dapagliflozin on oxidative stress, insulin resistance, and lipid metabolism.

The Safety and Efficacy of Combination Therapy of Dapagliflozin and Metformin in Patient with Type 2 Diabetes Mellitus: A Review Study

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class that approved by FDA for patient with type 2 DM. Dapagliflozin alone or in combination therapy with metformin provided effective glycemic control and HbA1c reduction, with minimal hypoglycemia and hypotension adverse effects. Objective: To evaluate the safety and efficacy of the combination therapy of dapagliflozin and metformin in type 2 diabetes mellitus patients. Methods: Research was conducted through MEDLINE and Embase databases in search of randomized controlled studies including dapagliflozin, sodium glucose co-transporter 2, metformin, and efficacy. Results: Forty seven articles were spotted, 3 randomized controlled studies were involved in this review. Dapagliflozin and metformin combination was found beneficial in HbA1c reduction equal to 20.7% - 31.5% from the baseline compared to patients on metformin alone. 40.6% of patients on combination therapy achieved the ADA recommended reduction in HbA1c to less than 7%. Moreover fasting plasma glucose level was reduced by 23.4 mg/dl from the baseline in the combination therapy compared to 5.9 mg/dl in metformin group. Body weight reduction was statistically significant (P Conclusion: The combination therapy of dapagliflozin and metformin found to be safe and effective in type 2 diabetes mellitus management with minimal adverse effects.

Meta-Analysis on Safety of Dapagliflozin in Patients with Type 2 Diabetes Mellitus

Objective: To evaluate the safety of dapagliflozin for Type 2 Diabetes Mellitus (T2DM). Methods: A systematic search of Pubmed, Embase, Cochrance Library, Web of Science, CNKI, Wanfang Data and VIP database for randomized controlled trials (RCTs) comparing dapagliflozin with placebo was performed up to February 2018. The index words included dapagliflozin, type 2 diabetes mellitus and randomized controlled trial. Results: A total of 19 RCTs involving 7704 participants were incorporated into the study. Compared with placebo, dapagliflozin did not increase the risk of hypoglycemia [OR = 1.14, 95%CI (0.95, 1.36), P = 0.17] and hypotension [OR = 1.43, 95%CI (0.94, 2.17), P = 0.10], but significantly increased the incidences of renal adverse events [OR = 1.57, 95%CI (1.17, 2.09), P = 0.002], genital tract infection [OR = 3.65, 95%CI (2.93, 4.56), P Conclusions: Generally, dapagliflozin had no risk of hypoglycemia and hypotension in patients with T2DM, but there were risks of renal adverse events and urogenital tract infection. Due to the limitations of this study, larger samples and RCTs with long-term follow-up are needed for further verification.

Dapagliflozin and Spironolactone Improved Clinical Symptoms and CV Outcomes in Patient with HF Preserved Ejection Fraction (HFpEF) in Hard-to-Reach Rural African Population: A Case Series

Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Result: The use of spironolactone and dapagliflozin was shown to be effective in improving the clinical outcome and reducing CV hospitalization rate and CV mortality in patients with heart failure preserved left ventricular ejection fraction (HFpEF). This is the case presentation of one patient with HFpEF with diastolic dysfunction grade 3, obesity grade 3, Type 2 Diabetes, and Atrial Fibrillation (permanent). In the case of a 76-year-old female after previous ineffective treatment, the initiation of Spironolactone and Dapagliflozin led to a rapid and marked improvement in the clinical conditions. Diastolic dysfunction was improved from stage III to stage I. Moreover, the initiation of spironolactone and dapagliflozin therapy avoided a referral for surgical intervention and interrupted a long series of hospitalizations for acute HF and prevented CV death. Conclusion: Based on our experience, we conclude that the treatment with spironolactone and dapagliflozin allows for better treatment optimization with a positive impact on the control of clinical outcomes and preventing CV death and CV hospitalization in HFpEF and related comorbidities in the African population, which is underrepresented in most of the trials.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction

Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory.The new hypoglycemic drug dapagliflozin has shown certain benefits,such as decreasing the risk of cardiovascular and renal events in patients with diabetes.Even so,until now,the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification.Here,we found that dapagliflozin lowered blood glucose levels,alleviated seminiferous tubule destruction,and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice.Moreover,the glucagon-like peptide-1 receptor(GLP-1R)antagonist exendin(9-39)had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice.We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2(BCL2)and X-linked inhibitor of apoptosis protein(XIAP)and inhibiting oxidative stress by enhancing the antioxidant status,including total antioxidant capacity,total superoxide dismutase(SOD)activity,and glutathione peroxidase(GPx)activity,as well as decreasing the level of 4-hydroxynonenal(4-HNE).Exendin(9-39)administration partially reversed these effects.Furthermore,dapagliflozin upregulated the glucagon-like peptide-1(GLP-1)level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog(Akt)phosphorylation in testicular tissue.Exendin(9-39)partially inhibited Akt phosphorylation.These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway.Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

达格列净对2型糖尿病患者经皮冠状动脉介入治疗术后对比剂肾病发病的影响

背景达格列净是治疗2型糖尿病(T2DM)的有效药物,还具有降低T2DM肾病进展风险、减少尿蛋白以及心脏保护等作用,然而,达格列净能否降低T2DM患者经皮冠状动脉介入治疗(PCI)术后对比剂肾病(CIN)发生率,目前尚不完全清楚。目的探讨达格列净对T2DM患者PCI术后CIN发病的影响。方法根据达格列净使用情况以1∶1倾向性匹配原则,回顾性连续纳入2021—2023年于天津市胸科医院心内科行PCI治疗的T2DM患者共484例为研究对象,其中达格列净组242例、对照组242例。收集2组患者PCI术前的临床资料并进行比较,同时记录2组患者PCI术前、PCI术后48 h及PCI术后1周的肾功能,包括血尿素氮(BUN)、血清肌酐(Scr)、肌酐清除率(Ccr)、胱抑素C(Cys-C)、β2微球蛋白(β2-MG)、中性粒细胞明胶酶相关载脂蛋白(NGAL)的变化。主要终点事件为CIN发病率,次要终点事件为PCI围术期肾功能的变化。采用多因素Logistic回归分析达格列净对T2DM患者PCI术后CIN发病的影响。结果达格列净组患者CIN发病率为6.2%,低于对照组患者的CIN发病率(12.0%),差异有统计学意义(χ^(2)=4.900,P=0.039);达格列净组患者CIN危险评分及B型钠尿肽高于对照组(P<0.05)。PCI术前、术后1周,2组患者BUN、Scr、Ccr、Cys-C、β2-MG、NGAL水平比较,差异均无统计学意义(P>0.05)。PCI术后48 h,达格列净组患者Cys-C、β2-MG、NGAL水平低于对照组(P<0.05)。多因素Logistic回归分析结果显示,CIN危险评分高(OR=1.213,95%CI=1.085~1.358,P=0.001)、B型钠尿肽水平升高(OR=3.940,95%CI=1.479~10.494,P=0.006)是T2DM患者PCI术后CIN发病的独立危险因素,使用达格列净(OR=0.338,95%CI=0.159~0.717,P=0.005)是T2DM患者PCI术后CIN发病的独立保护因素。结论使用达格列净是T2DM患者PCI术后CIN发病的独立保护因素,达格列净并不增加T2DM患者PCI术后急性肾损伤的发病风险,并可能降低CIN的发生率。

达格列净与二甲双胍、甘精胰岛素联合治疗对老年2型糖尿病患者血糖水平、胰岛素指标的影响

目的探讨达格列净与二甲双胍、甘精胰岛素联合治疗老年2型糖尿病的效果。方法将80例老年2型糖尿病患者随机分为两组。两组均采用二甲双胍治疗,在此基础上对照组采用甘精胰岛素治疗,观察组采用达格列净联合甘精胰岛素治疗。比较两组的血糖水平、胰岛素相关指标、不良反应发生率。结果治疗后,观察组血糖水平低于对照组,胰岛素相关指标优于对照组(P<0.05)。观察组不良反应发生率为15.00%,与对照组的12.50%比较无统计学差异(P>0.05)。结论达格列净与二甲双胍、甘精胰岛素联合治疗老年2型糖尿病的效果较好,可强化患者血糖调控,改善胰岛功能,安全可靠,临床价值显著。

益肾化湿颗粒联合达格列净治疗糖尿病肾病脾肾气虚证临床研究

目的:观察益肾化湿颗粒联合达格列净治疗糖尿病肾病(DN)脾肾气虚证的临床疗效及对血小板反应蛋白1 (TSP-1)、可溶性Axl受体酪氨酸激酶(sAxl)水平的影响。方法:采用随机数字表法将88例DN脾肾气虚证患者分为对照组与观察组各44例。对照组给予单纯达格列净治疗,观察组给予益肾化湿颗粒联合达格列净治疗。比较2组治疗前后中医证候积分、肾脏功能指标、血糖指标、TSP-1、sAxl水平,评估2组临床疗效及不良反应发生情况。结果:治疗后,观察组总有效率93.18%,高于对照组77.27%(P<0.05)。治疗后,2组中医证候积分、尿白蛋白/肌酐比值(UACR)、尿白蛋白排泄率(UAER)、空腹血糖(FBG)、餐后2 h血糖(P2hBG)、糖化血红蛋白(HbA1c)、 TSP-1、 sAxl水平均低于治疗前(P<0.05),肾小球滤过率(eGFR)水平高于治疗前(P<0.05),且观察组治疗后UACR、UAER、TSP-1、sAxl水平及血糖指标均低于对照组(P<0.05),eGFR水平高于对照组(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:益肾化湿颗粒联合达格列净治疗DN脾肾气虚证疗效显著,能有效改善患者肾脏功能,控制血糖,降低TSP-1、sAxl水平,安全性较高。

达格列净对糖尿病肾病大鼠肾脏保护作用机制研究

目的 探讨达格列净对糖尿病肾病(diabeticnephropathy,DN)大鼠的肾脏保护作用及对AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路表达的影响。方法 SPF级Wistar雄性大鼠40只,随机分为正常组、模型组、低剂量组和高剂量组,每组各10只。成功制备DN模型后,正常组大鼠给予普通饲料+生理盐水灌胃;模型组大鼠给予高糖高脂饲料+生理盐水灌胃;低剂量组大鼠给予高糖高脂饲料+达格列净1mg/(kg·d)灌胃;高剂量组大鼠给予高糖高脂饲料+达格列净10mg/(kg·d)灌胃。各组大鼠连续干预12周。比较各组大鼠的肾功能指标、肾脏病理组织变化、p-AMPK和p-mTOR蛋白表达、Ⅰ型胶原(collagen typeⅠ,COLⅠ)、Ⅳ型胶原(collagen typeⅣ,COLⅣ)、纤维连接蛋白(fibronectin,FN)水平。结果 模型组、低剂量组和高剂量组大鼠的血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,SCr)、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著高于正常组,p-AMPK蛋白表达显著低于正常组(P<0.05);低剂量组和高剂量组大鼠的BUN、SCr、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著低于模型组,p-AMPK蛋白表达显著高于模型组(P<0.05);高剂量组大鼠的BUN、SCr、24h尿蛋白定量、p-mTOR蛋白表达、COLⅠ、COLⅣ和FN水平均显著低于低剂量组,p-AMPK蛋白表达显著高于低剂量组(P<0.05)。结论 达格列净对DN大鼠具有良好的肾脏保护作用,其机制可能与调节AMPK/mTOR信号通路表达有关。

Dapagliflozin对照安慰剂治疗2型糖尿病的系统评价

目的评价Dapagliflozin治疗T2DM的疗效和安全性。方法检索PubMed、Embase、Medline、Cochrane图书馆、CNKI、万方、维普、CBM 8个数据库,按Cochrane系统评价的方法评价纳入研究质量,并使用RevMan 5.2软件进行Meta分析。结果共纳入12项研究,4914例患者。与安慰剂相比,Dapagliflozin降低HbA1c(WMD=-0.58,95%CI:-0.63^-0.53,P<0.00001)、FPG(WMD=-1.23,95%CI:-1.45,-1.00,P<0.00001)和体重(WMD=-1.77,95%CI:-1.95^-1.58,P<0.00001)疗效差异均有统计学意义。安全性方面二者发生总不良反应事件(RR=1.03,95%CI:0.99~1.07,P=0.09)和低血糖事件的风险差异均无统计学意义(RR=0.96,95%CI:0.74~1.25,P=0.77)。Dapagliflozin与安慰剂比较发生生殖道真菌感染(RR=3.39,95%CI:2.56~4.50,P=0.0007)及尿路感染(RR=1.45,95%CI:1.17~1.80,P<0.00001)的风险升高。结论 Dapagliflozin与安慰剂比较能更为显著的改善T2DM患者血糖控制,减轻体重;总不良反应事件和低血糖事件发生率与安慰剂相当,可增加患者泌尿系统感染及生殖系统感染的风险。

治疗2型糖尿病的新型化合物——Dapagliflozin

目的:介绍治疗2型糖尿病的新型化合物Dapagliflozin。方法:根据文献,对Dapagliflozin的作用机制、药动学、临床疗效、不良反应等方面的信息进行综述。结果:Dapagliflozin通过抑制肾钠-葡萄糖协同转运蛋白2,抑制血糖的重吸收,从而调节体内血糖水平;其主要经尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A9代谢,患者口服后体内t1/2达11h以上;其可显著降低患者糖化血红蛋白水平与体重;其不良反应主要包括恶心、眩晕和泌尿生殖道感染等,一般可耐受,且发生率较低。结论:Dapagliflozin作用机制明确,每日1次口服治疗2型糖尿病的安全性与有效性较好,具备良好的应用前景。