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 tot...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.展开更多
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 pr...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.展开更多
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 se...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.展开更多
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 ...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 HbA<sub>1c</sub> 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 HbA<sub>1c</sub> 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 HbA<sub>1c</sub> 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.展开更多
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 random...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.展开更多
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 Re...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.展开更多
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 c...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.展开更多
目的探讨达格列净治疗2型糖尿病(T2DM)合并高尿酸血症的疗效和安全性。方法122例2型糖尿病患者合并无症状高尿酸血症患者,随机分为对照组和观察组。对照组60例经过口服二甲双胍片1片tid联合磷酸西格列汀片1片QD治疗。观察组62例经过口...目的探讨达格列净治疗2型糖尿病(T2DM)合并高尿酸血症的疗效和安全性。方法122例2型糖尿病患者合并无症状高尿酸血症患者,随机分为对照组和观察组。对照组60例经过口服二甲双胍片1片tid联合磷酸西格列汀片1片QD治疗。观察组62例经过口服二甲双胍1片tid联合达格列净片1片QD治疗。两组患者均经过12周治疗。比较两组患者治疗前后的空腹血糖水平(FPG)、餐后2 h血糖水平(2 h PG)、糖化血红蛋白(HbAlc)、血尿酸(BUA)、血肌酐(Scr)、尿素氮(BUN)和不良反应发生情况。结果对照组1例失访。观察组2例未完成随访,其中1例因发生泌尿系感染,1例因胃肠道不耐受退出试验。治疗12周后观察组FPG、2 h PG、HbAlc、BUA和BUN均有显著性下降,而治疗后血糖达标率,Scr和不良反应两组无统计学差异。结论口服达格列净片治疗2型糖尿病合并无症状高尿酸血症能有效控制血糖,降低血尿酸水平,延缓相关并发症,具有一定的临床推广应用价值。展开更多
目的探究对老年慢性心力衰竭合并2型糖尿病(Diabetes Mellitus Type 2,T2DM)及高尿酸血症患者采用达格列净和标准抗心衰及降糖方案结合治疗后效果。方法随机选取2021年6月—2022年6月广州市花都区人民医院收治的心力衰竭合并T2DM及高尿...目的探究对老年慢性心力衰竭合并2型糖尿病(Diabetes Mellitus Type 2,T2DM)及高尿酸血症患者采用达格列净和标准抗心衰及降糖方案结合治疗后效果。方法随机选取2021年6月—2022年6月广州市花都区人民医院收治的心力衰竭合并T2DM及高尿酸血症患者120例为研究对象,采用随机数表法分成对照组(60例)、观察组(60例)。对照组采取标准抗心衰及降糖方案,观察组在对照组基础上采取达格列净,对比临床效果。结果观察组氨基末端脑钠肽前体(N Terminal Pro B Type Natriuretic Peptide,NT-proBNP)为(519.36±107.52)ng/L、血尿酸为(346.17±42.15)μmol/L低于对照组,差异有统计学意义(t=2.020、4.245,P<0.05)。观察组血脂改善更好,左室舒张末容积、左室收缩末容积、舒张早期二尖瓣血流速度/二尖瓣环运动速度(the Ratio of Early Diastolic Transmitral Flow Velocity to Mitral Annular Velocity,E/e’)低于对照组,左室射血分数高于对照组,差异有统计学意义(P<0.05)。观察组主要终点事件、次要终点事件、痛风发作率低于对照组,差异有统计学意义(P<0.05)。两组药物不良反应率对比,差异无统计学意义(P>0.05)。结论针对老年慢性心力衰竭合并T2DM及高尿酸血症患者,采用达格列净联合标准抗心衰及降糖方案,能改善血脂、心功能等指标水平,预后效果以及安全性较高。展开更多
基金Suqian Science and Technology Plan Project(No.Z2019178)。
文摘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.
文摘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.
基金Supported by Major Scientific Research Program of The Affiliated Hospital of Inner Mongolia Medical University,No. NYFY ZD 001
文摘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.
文摘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 HbA<sub>1c</sub> 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 HbA<sub>1c</sub> 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 HbA<sub>1c</sub> 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.
文摘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.
文摘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.
基金This work was supported by the National Natural Science Foundation of China(81901535 and 82071698)the Natural Science Foundation of Beijing Municipality(7222208)the National Key Research&Developmental Program of China(2021YFC2700203).
文摘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.
文摘目的探讨达格列净治疗2型糖尿病(T2DM)合并高尿酸血症的疗效和安全性。方法122例2型糖尿病患者合并无症状高尿酸血症患者,随机分为对照组和观察组。对照组60例经过口服二甲双胍片1片tid联合磷酸西格列汀片1片QD治疗。观察组62例经过口服二甲双胍1片tid联合达格列净片1片QD治疗。两组患者均经过12周治疗。比较两组患者治疗前后的空腹血糖水平(FPG)、餐后2 h血糖水平(2 h PG)、糖化血红蛋白(HbAlc)、血尿酸(BUA)、血肌酐(Scr)、尿素氮(BUN)和不良反应发生情况。结果对照组1例失访。观察组2例未完成随访,其中1例因发生泌尿系感染,1例因胃肠道不耐受退出试验。治疗12周后观察组FPG、2 h PG、HbAlc、BUA和BUN均有显著性下降,而治疗后血糖达标率,Scr和不良反应两组无统计学差异。结论口服达格列净片治疗2型糖尿病合并无症状高尿酸血症能有效控制血糖,降低血尿酸水平,延缓相关并发症,具有一定的临床推广应用价值。
文摘目的探究对老年慢性心力衰竭合并2型糖尿病(Diabetes Mellitus Type 2,T2DM)及高尿酸血症患者采用达格列净和标准抗心衰及降糖方案结合治疗后效果。方法随机选取2021年6月—2022年6月广州市花都区人民医院收治的心力衰竭合并T2DM及高尿酸血症患者120例为研究对象,采用随机数表法分成对照组(60例)、观察组(60例)。对照组采取标准抗心衰及降糖方案,观察组在对照组基础上采取达格列净,对比临床效果。结果观察组氨基末端脑钠肽前体(N Terminal Pro B Type Natriuretic Peptide,NT-proBNP)为(519.36±107.52)ng/L、血尿酸为(346.17±42.15)μmol/L低于对照组,差异有统计学意义(t=2.020、4.245,P<0.05)。观察组血脂改善更好,左室舒张末容积、左室收缩末容积、舒张早期二尖瓣血流速度/二尖瓣环运动速度(the Ratio of Early Diastolic Transmitral Flow Velocity to Mitral Annular Velocity,E/e’)低于对照组,左室射血分数高于对照组,差异有统计学意义(P<0.05)。观察组主要终点事件、次要终点事件、痛风发作率低于对照组,差异有统计学意义(P<0.05)。两组药物不良反应率对比,差异无统计学意义(P>0.05)。结论针对老年慢性心力衰竭合并T2DM及高尿酸血症患者,采用达格列净联合标准抗心衰及降糖方案,能改善血脂、心功能等指标水平,预后效果以及安全性较高。
