目的评价Canagliflozin治疗2型糖尿病的疗效和安全性。方法计算机检索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Rev Man 5.2软件进行Meta分析。结...目的评价Canagliflozin治疗2型糖尿病的疗效和安全性。方法计算机检索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Rev Man 5.2软件进行Meta分析。结果共纳入8项随机对照试验,共计4 503例患者。Meta分析结果显示,Canagliflozin与安慰剂相比,降低糖化血红蛋白(HbA1c)[WMD=-0.74,95%CI(-0.84,-0.64),P<0.01]、空腹血糖(FPG)[WMD=-31.03,95%CI(-32.06,-25.50),P<0.01]和体质量[WMD=-2.43,95%CI(-2.77,-2.08),P<0.01]的疗效差异均有统计学意义,安全性方面,Canagliflozin与安慰剂相比总不良反应发生率[RR=1.16,95%CI(1.02,1.32),P=0.02]高于安慰剂组,发生低血糖事件的风险未高于安慰剂组[RR=1.35,95%CI(0.68,2.71),P=0.39]。结论与安慰剂比较,Canagliflozin可有效降低2型糖尿病患者HbA1c及空腹血糖,可明显降低体质量;Canagliflozin不良反应发生率略高,发生低血糖风险较低。展开更多
Canagliflozin(CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter(SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking...Canagliflozin(CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter(SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus.展开更多
OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and th...OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.展开更多
Objective:To investigate the effects of cagliazin,a sodium-glucose cotransporter 2 inhibitor(SGLT-2I),on ventricular remodeling in spontaneously hypertensive rats(SHR)through renin angiotensin system(RAS)and transform...Objective:To investigate the effects of cagliazin,a sodium-glucose cotransporter 2 inhibitor(SGLT-2I),on ventricular remodeling in spontaneously hypertensive rats(SHR)through renin angiotensin system(RAS)and transforming growth factor-β1(TGF-β1).Methods:The experiment was divided into 4 groups:normal blood pressure control group,SHR group,cagliet net low-dose group(30mg/kg),cagliet net high-dose group(60mg/kg),once a day for 8 weeks.Normal blood pressure rats(WKY)were used as the control group to measure blood pressure with tail sleeve sphygmomanometer(BP)and blood glucose level was measured with glucose meter Cardiac function was evaluated by echocardiography,cell area of left ventricle was evaluated by histomorphology,real-time quantitative polymerase chain reaction and protein imprinting hybridization were used to detect TGF-β1 Smad4 renin from type I collagen(Col1a)type III collagen(Col3a)matrix metalloproteinase 2(MMP-2)Expression results of angiotensin II1 type receptor 1(AGTR1)and Angiotensin II2 type receptor 2(AGTR2).Results:After 8 weeks of administration,the cardiac weight/body weight ratio(HW/BW)of left ventricular weight/heart weight ratio(LVW/HW)of kaglinet low-dose group and high-dose group was statistically significant compared with that of spontaneous hypertensive rats(P<);Compared with SHRs,the expression of Col1a,Col3a,MMP2,TGF-β1,Smad4,Renin AGTR1 was significantly down-regulated and the expression of AGTR2 was up-regulated in cagliet net low-dose and high-dose groups Conclusions:Cagliazin can improve hypertension-induced cardiac remodeling by regulating RAS and TGF-β1/Smad signaling pathways.Conclusion:From the results,canaglifozin was found to ameliorate pressure overload-induced cardiac remodeling by regulating the RAS and TGF-β1/Smad signaling pathway.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
The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduc...The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin(BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase(p AMPK) expression and decreased tumor necrosis factor alpha(TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.展开更多
文摘目的评价Canagliflozin治疗2型糖尿病的疗效和安全性。方法计算机检索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Rev Man 5.2软件进行Meta分析。结果共纳入8项随机对照试验,共计4 503例患者。Meta分析结果显示,Canagliflozin与安慰剂相比,降低糖化血红蛋白(HbA1c)[WMD=-0.74,95%CI(-0.84,-0.64),P<0.01]、空腹血糖(FPG)[WMD=-31.03,95%CI(-32.06,-25.50),P<0.01]和体质量[WMD=-2.43,95%CI(-2.77,-2.08),P<0.01]的疗效差异均有统计学意义,安全性方面,Canagliflozin与安慰剂相比总不良反应发生率[RR=1.16,95%CI(1.02,1.32),P=0.02]高于安慰剂组,发生低血糖事件的风险未高于安慰剂组[RR=1.35,95%CI(0.68,2.71),P=0.39]。结论与安慰剂比较,Canagliflozin可有效降低2型糖尿病患者HbA1c及空腹血糖,可明显降低体质量;Canagliflozin不良反应发生率略高,发生低血糖风险较低。
文摘Canagliflozin(CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter(SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus.
基金The project supported by National Natural Science Foundation of China(81373460)by the Natural Science Foundation of Guangdong Province(2014A030313744)
文摘OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.
基金National Natural Science Foundation of China(No.31570949)。
文摘Objective:To investigate the effects of cagliazin,a sodium-glucose cotransporter 2 inhibitor(SGLT-2I),on ventricular remodeling in spontaneously hypertensive rats(SHR)through renin angiotensin system(RAS)and transforming growth factor-β1(TGF-β1).Methods:The experiment was divided into 4 groups:normal blood pressure control group,SHR group,cagliet net low-dose group(30mg/kg),cagliet net high-dose group(60mg/kg),once a day for 8 weeks.Normal blood pressure rats(WKY)were used as the control group to measure blood pressure with tail sleeve sphygmomanometer(BP)and blood glucose level was measured with glucose meter Cardiac function was evaluated by echocardiography,cell area of left ventricle was evaluated by histomorphology,real-time quantitative polymerase chain reaction and protein imprinting hybridization were used to detect TGF-β1 Smad4 renin from type I collagen(Col1a)type III collagen(Col3a)matrix metalloproteinase 2(MMP-2)Expression results of angiotensin II1 type receptor 1(AGTR1)and Angiotensin II2 type receptor 2(AGTR2).Results:After 8 weeks of administration,the cardiac weight/body weight ratio(HW/BW)of left ventricular weight/heart weight ratio(LVW/HW)of kaglinet low-dose group and high-dose group was statistically significant compared with that of spontaneous hypertensive rats(P<);Compared with SHRs,the expression of Col1a,Col3a,MMP2,TGF-β1,Smad4,Renin AGTR1 was significantly down-regulated and the expression of AGTR2 was up-regulated in cagliet net low-dose and high-dose groups Conclusions:Cagliazin can improve hypertension-induced cardiac remodeling by regulating RAS and TGF-β1/Smad signaling pathways.Conclusion:From the results,canaglifozin was found to ameliorate pressure overload-induced cardiac remodeling by regulating the RAS and TGF-β1/Smad signaling pathway.
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.
基金supported by National Natural Science Foundation of China(No.81373460)Natural Science Foundation of Guangdong Province(No.2014A030313744)+1 种基金Shenzhen Science and Technology R&D Foundation(SGLH20121008144756945)China Scholarship Council(201308440130)
文摘The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin(BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase(p AMPK) expression and decreased tumor necrosis factor alpha(TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.
