鲁格列净治疗2型糖尿病疗效及安全性的Meta分析
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摘要
目的系统评价鲁格列净治疗2型糖尿病的疗效及安全性。方法计算机检索Cochrane图书馆、PubMed、EMBase、CBM、CNKI、万方数据库、维普数据库,收集鲁格列净治疗2型糖尿病的随机对照试验(RCT),提取资料并进行质量评价后,采用Rev Man5. 3统计软件进行Meta分析。结果共纳入5项RCT,均来源于英文数据库,合计764例患者。Meta分析结果显示与安慰剂组相比,鲁格列净组糖化血红蛋白[WMD=-0. 94,95%CI(-1. 02,-0. 87),P <0. 01]、空腹血糖[WMD=-33. 09,95%CI(-35. 93,-30. 25),P <0. 01]下降;药物不良反应发生率[RR=1. 92,95%CI(1. 30,2. 83),P <0. 01]、尿频发生率[RR=2. 41,95%CI(1. 09,5. 37),P=0. 03]增多;不良事件发生率[RR=1. 01,95%CI (0. 88,1. 15),P=0. 91]、低血糖发生率[RR=1. 36,95%CI(0. 76,2. 42),P=0. 30]、泌尿系统感染发生率[RR=2. 50,95%CI(0. 30,21. 11),P=0. 40]、生殖系统感染发生率[RR=1. 72,95%CI(0. 50,5. 89),P=0. 39]、肾功能异常发生率[RR=1. 18,95%CI(0. 69,2. 02),P=0. 53]和体积减少相关不良反应发生率[RR=1. 34,95%CI(0. 47,3. 80),P=0. 59]差异无统计学意义。结论在2型糖尿病不同治疗周期,鲁格列净均能有效改善患者的糖化血红蛋白和空腹血糖,不会导致严重不良事件以及特殊不良反应发生,一般不良反应轻微可耐受,用药较为安全。
Objective To systematically evaluate the efficacy and safety of luseogliflozin in treatment of type2 diabetes mellitus( T2DM). Methods The randomized controlled trials( RCTs) of luseogliflozin for T2DM were searched from Cochrane Library,PubMed,EMBase,CBM,CNKI,Wanfang and VIP databases using a computer.The data were extracted and the quality of the included studies was assessed. RevMan5. 3 statistical software was used for Meta-analysis. Results A total of 764 cases in 5 RCTs were included,which were from English databases. Compared with those in the placebo group,HbA1c [WMD =-0. 94,95% CI(-1. 02,-0. 87),P < 0. 01]and fasting plasma glucose [WMD =-33. 09,95% CI(-35. 93,-30. 25),P < 0. 01] in the luseogliflozin group were decreased; The incidence of adverse reactions [RR = 1. 92,95% CI( 1. 30,2. 83),P < 0. 01]and frequency of urinary frequency [RR = 2. 41,95% CI( 1. 09,5. 37),P = 0. 03] in the luseogliflozin group were increased. There were no significant differences in the incidence rates of adverse events [RR = 1. 01,95% CI( 0. 88,1. 15),P = 0. 91],hypoglycemia [RR = 1. 36,95% CI( 0. 76,2. 42),P = 0. 30],urinary tract infections [RR = 2. 50,95% CI( 0. 30,21. 11),P = 0. 40],reproductive system infections [RR = 1. 72,95% CI( 0. 50,5. 89),P = 0. 39],abnormal renal function[RR = 1. 18,95% CI( 0. 69,2. 02),P = 0. 53] and volume reduction related adverse reactions[RR = 1. 34,95% CI( 0. 47,3. 80),P = 0. 59] between the two groups. Conclusion In different treatment cycles of T2DM,luseogliflozin can effectively improve HbA1c and fasting plasma glucose,but leads to no serious adverse events and special adverse reactions. The adverse reactions are common,mild and tolerable,and the medication is safe.
Objective To systematically evaluate the efficacy and safety of luseogliflozin in treatment of type2 diabetes mellitus( T2DM). Methods The randomized controlled trials( RCTs) of luseogliflozin for T2DM were searched from Cochrane Library,PubMed,EMBase,CBM,CNKI,Wanfang and VIP databases using a computer.The data were extracted and the quality of the included studies was assessed. RevMan5. 3 statistical software was used for Meta-analysis. Results A total of 764 cases in 5 RCTs were included,which were from English databases. Compared with those in the placebo group,HbA1c [WMD =-0. 94,95% CI(-1. 02,-0. 87),P < 0. 01]and fasting plasma glucose [WMD =-33. 09,95% CI(-35. 93,-30. 25),P < 0. 01] in the luseogliflozin group were decreased; The incidence of adverse reactions [RR = 1. 92,95% CI( 1. 30,2. 83),P < 0. 01]and frequency of urinary frequency [RR = 2. 41,95% CI( 1. 09,5. 37),P = 0. 03] in the luseogliflozin group were increased. There were no significant differences in the incidence rates of adverse events [RR = 1. 01,95% CI( 0. 88,1. 15),P = 0. 91],hypoglycemia [RR = 1. 36,95% CI( 0. 76,2. 42),P = 0. 30],urinary tract infections [RR = 2. 50,95% CI( 0. 30,21. 11),P = 0. 40],reproductive system infections [RR = 1. 72,95% CI( 0. 50,5. 89),P = 0. 39],abnormal renal function[RR = 1. 18,95% CI( 0. 69,2. 02),P = 0. 53] and volume reduction related adverse reactions[RR = 1. 34,95% CI( 0. 47,3. 80),P = 0. 59] between the two groups. Conclusion In different treatment cycles of T2DM,luseogliflozin can effectively improve HbA1c and fasting plasma glucose,but leads to no serious adverse events and special adverse reactions. The adverse reactions are common,mild and tolerable,and the medication is safe.
引文
1 World Health Organization.Global report on diabetes[R].Geneva:WHO,2016.
2王晔,刘文东,王芳.2型糖尿病治疗药物应用进展[J].药学进展,2017,41(6):434-443.
3 Chao EC.SGLT-2 inhibitors:A New Mechanism for Glycemic Control[J].Clin Diabetes,2014,32(1):4-11.
4罗建设,李桂红.糖尿病患者自我管理及其干预的研究进展[J].中国临床新医学,2015,8(4):384-387.
5黎风,何梅,刘福.SGLT2抑制剂治疗2型糖尿病伴肾损害患者的安全性和有效性的Meta分析[J].中国新药与临床杂志,2017,36(9):545-551.
6 Seidu S,Kunutsor SK,Cos X,et al.SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment:A systematic review and meta-analysis[J].Prim Care Diabetes,2018,12(3):265-283.
7刘锴,宋海燕.钠-葡萄糖协同转运蛋白2抑制剂治疗糖尿病研究新进展[J].中国糖尿病杂志,2014,22(3):280-283.
8汪武卫,陈洁.SGLT2抑制剂批准新药的发现及合成评述[J].中国新药杂志,2016,25(6):650-658.
9孙永,田琳,吴让兵,等.2型糖尿病治疗新药恩格列净的研究现状[J].中国糖尿病杂志,2018,26(6):523-528.
10 Marín-Pe1alver JJ,Martín-Timón I,Sevillano-Collantes C,et al.Update on the treatment of type 2 diabetes mellitus[J].World J Diabetes,2016,7(17):354-395.
11陈勇彬.社区糖尿病患者降糖药物应用情况调查分析[J].中国临床新医学,2013,6(3):248-250.
12董松涛,董占军.钠-葡萄糖共转运蛋白2抑制剂作用机制及临床应用研究进展[J].国际药学研究杂志,2017,44(9):828-834.
13 Markham A,Elkinson S.Luseogliflozin:first global approval[J].Drugs,2014,74(8):945-950.
14 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus:a
12-week,randomized,placebo-controlled,phase II study[J].Curr Med Res Opin,2014,30(7):1219-1230.
15 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus:a randomized,double-blind,placebo-controlled,phase 3 study[J].Curr Med Res Opin,2014,30(7):1245-1255.
16 Seino Y,Sasaki T,Fukatsu A,et al.Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus:a 12-week,randomized,double-blind,placebo-controlled,phaseⅡstudy[J].Curr Med Res Opin,2015,30(7):1231-1244.
17 Haneda M,Seino Y,Inagaki N,et al.Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus[J].Clin Ther,2016,38(1):66-88.e20.
18 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin added to insulin therapy in Japanese patients with type 2 diabetes:a multicenter,52-week,clinical study with a 16-week,doubleblind period and a 36-week,open-label period[J].Curr Med Res Opin,2018,34(6):981-994.
19 Yamamoto K,Uchida S,Kitano K,et al.TS-071 is a novel,potent and selective renal sodium-glucose cotransporter 2(SGLT2)inhibitor with anti-hyperglycaemic activity[J].Br J Pharmacol,2011,164(1):181-191.
20 Samukawa Y,Mutoh M,Chen S,et al.Mechanism-based pharmacokinetic-pharmacodynamic modeling of luseogliflozin,a sodium glucose co-transporter 2 inhibitor,in Japanese patients with type 2 diabetes mellitus[J].Biol Pharm Bull,2017,40(8):1207-1218.
21 Kaneto H,Obata A,Kimura T,et al.Beneficial effects of sodium-glucose cotransporter 2 inhibitors for preservation of pancreaticβ-cell function and reduction of insulin resistance[J].J Diabetes,2017,9(3):219-225.
22 Okauchi S,Shimoda M,Obata A,et al.Protective effects of SGLT2 inhibitor luseogliflozin on pancreaticβ-cells in obese type 2 diabetic db/db mice[J].Biochem Biophys Res Commun,2016,470(3):772-782.
23纪立农,郭立新,郭晓蕙,等.钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂临床合理应用中国专家建议[J].中国糖尿病杂志,2016,24(10):865-870.
24 Chou YM,Seak CJ,Goh ZNL,et al.Euglycemic diabetic ketoacidosis caused by dapagliflozin:A case report[J].Medicine(Baltimore),2018,97(25):e11056.
25 Qiu H,Novikov A,Vallon V.Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors:Basic mechanisms and therapeutic perspectives[J].Diabetes Metab Res Rev,2017,33(5):e2886.
26 Samukawa Y,Haneda M,Seino Y,et al.Pharmacokinetics and Pharmacodynamics of Luseogliflozin,a Selective SGLT2 Inhibitor,in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment[J].Clin Pharmacol Drug Dev,2018,7(8):820-828.
27 van Baar MJB,van Ruiten CC,Muskiet MHA,et al.SGLT2 Inhibitors in Combination Therapy:From Mechanisms to Clinical Considerations in Type 2 Diabetes Management[J].Diabetes Care,2018,41(8):1543-1556.
28 Whalen K,Miller S,Onge ES.The Role of Sodium-Glucose CoTransporter 2 Inhibitors in the Treatment of Type 2 Diabetes[J].Clin Ther,2015,37(6):1150-1166.
29 Seino Y,Kaku K,Inagaki N,et al.Fifty-two-week long-term clinical study of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise[J].Endocr J,2015,62(7):593-603.
30 Morrow LA,Guttierrez MJ,Tanaka Y,et al.Luseogliflozin(TS-071),a novel,potent,and selective inhibitor of SGLT2 is safe and well-tolerated in type 2 diabetes mellitus and showed dosedependent PK/PDin both US/Japanese ethnicities[J].Diabetologia,2012,55:S304.
2王晔,刘文东,王芳.2型糖尿病治疗药物应用进展[J].药学进展,2017,41(6):434-443.
3 Chao EC.SGLT-2 inhibitors:A New Mechanism for Glycemic Control[J].Clin Diabetes,2014,32(1):4-11.
4罗建设,李桂红.糖尿病患者自我管理及其干预的研究进展[J].中国临床新医学,2015,8(4):384-387.
5黎风,何梅,刘福.SGLT2抑制剂治疗2型糖尿病伴肾损害患者的安全性和有效性的Meta分析[J].中国新药与临床杂志,2017,36(9):545-551.
6 Seidu S,Kunutsor SK,Cos X,et al.SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment:A systematic review and meta-analysis[J].Prim Care Diabetes,2018,12(3):265-283.
7刘锴,宋海燕.钠-葡萄糖协同转运蛋白2抑制剂治疗糖尿病研究新进展[J].中国糖尿病杂志,2014,22(3):280-283.
8汪武卫,陈洁.SGLT2抑制剂批准新药的发现及合成评述[J].中国新药杂志,2016,25(6):650-658.
9孙永,田琳,吴让兵,等.2型糖尿病治疗新药恩格列净的研究现状[J].中国糖尿病杂志,2018,26(6):523-528.
10 Marín-Pe1alver JJ,Martín-Timón I,Sevillano-Collantes C,et al.Update on the treatment of type 2 diabetes mellitus[J].World J Diabetes,2016,7(17):354-395.
11陈勇彬.社区糖尿病患者降糖药物应用情况调查分析[J].中国临床新医学,2013,6(3):248-250.
12董松涛,董占军.钠-葡萄糖共转运蛋白2抑制剂作用机制及临床应用研究进展[J].国际药学研究杂志,2017,44(9):828-834.
13 Markham A,Elkinson S.Luseogliflozin:first global approval[J].Drugs,2014,74(8):945-950.
14 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus:a
12-week,randomized,placebo-controlled,phase II study[J].Curr Med Res Opin,2014,30(7):1219-1230.
15 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus:a randomized,double-blind,placebo-controlled,phase 3 study[J].Curr Med Res Opin,2014,30(7):1245-1255.
16 Seino Y,Sasaki T,Fukatsu A,et al.Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus:a 12-week,randomized,double-blind,placebo-controlled,phaseⅡstudy[J].Curr Med Res Opin,2015,30(7):1231-1244.
17 Haneda M,Seino Y,Inagaki N,et al.Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus[J].Clin Ther,2016,38(1):66-88.e20.
18 Seino Y,Sasaki T,Fukatsu A,et al.Efficacy and safety of luseogliflozin added to insulin therapy in Japanese patients with type 2 diabetes:a multicenter,52-week,clinical study with a 16-week,doubleblind period and a 36-week,open-label period[J].Curr Med Res Opin,2018,34(6):981-994.
19 Yamamoto K,Uchida S,Kitano K,et al.TS-071 is a novel,potent and selective renal sodium-glucose cotransporter 2(SGLT2)inhibitor with anti-hyperglycaemic activity[J].Br J Pharmacol,2011,164(1):181-191.
20 Samukawa Y,Mutoh M,Chen S,et al.Mechanism-based pharmacokinetic-pharmacodynamic modeling of luseogliflozin,a sodium glucose co-transporter 2 inhibitor,in Japanese patients with type 2 diabetes mellitus[J].Biol Pharm Bull,2017,40(8):1207-1218.
21 Kaneto H,Obata A,Kimura T,et al.Beneficial effects of sodium-glucose cotransporter 2 inhibitors for preservation of pancreaticβ-cell function and reduction of insulin resistance[J].J Diabetes,2017,9(3):219-225.
22 Okauchi S,Shimoda M,Obata A,et al.Protective effects of SGLT2 inhibitor luseogliflozin on pancreaticβ-cells in obese type 2 diabetic db/db mice[J].Biochem Biophys Res Commun,2016,470(3):772-782.
23纪立农,郭立新,郭晓蕙,等.钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂临床合理应用中国专家建议[J].中国糖尿病杂志,2016,24(10):865-870.
24 Chou YM,Seak CJ,Goh ZNL,et al.Euglycemic diabetic ketoacidosis caused by dapagliflozin:A case report[J].Medicine(Baltimore),2018,97(25):e11056.
25 Qiu H,Novikov A,Vallon V.Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors:Basic mechanisms and therapeutic perspectives[J].Diabetes Metab Res Rev,2017,33(5):e2886.
26 Samukawa Y,Haneda M,Seino Y,et al.Pharmacokinetics and Pharmacodynamics of Luseogliflozin,a Selective SGLT2 Inhibitor,in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment[J].Clin Pharmacol Drug Dev,2018,7(8):820-828.
27 van Baar MJB,van Ruiten CC,Muskiet MHA,et al.SGLT2 Inhibitors in Combination Therapy:From Mechanisms to Clinical Considerations in Type 2 Diabetes Management[J].Diabetes Care,2018,41(8):1543-1556.
28 Whalen K,Miller S,Onge ES.The Role of Sodium-Glucose CoTransporter 2 Inhibitors in the Treatment of Type 2 Diabetes[J].Clin Ther,2015,37(6):1150-1166.
29 Seino Y,Kaku K,Inagaki N,et al.Fifty-two-week long-term clinical study of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise[J].Endocr J,2015,62(7):593-603.
30 Morrow LA,Guttierrez MJ,Tanaka Y,et al.Luseogliflozin(TS-071),a novel,potent,and selective inhibitor of SGLT2 is safe and well-tolerated in type 2 diabetes mellitus and showed dosedependent PK/PDin both US/Japanese ethnicities[J].Diabetologia,2012,55:S304.