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,demonstra...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.展开更多
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
BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCT...BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.展开更多
基金Supported by General Medical Research Fund Project,No.TYYLKYJJ-2022-025.
文摘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.
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BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.
