达格列净与2型糖尿病患者泌尿生殖系统感染相关性的Meta分析
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摘要
目的系统评价2型糖尿病患者服用达格列净后出现泌尿生殖系统感染的风险,为临床提供用药参考。方法计算机检索PubMed、EMbase、The Cochrane Library、Clinical Trials数据库,查找关于达格列净与泌尿生殖系统感染的相关临床研究,检索时限均为从建库至2018年1月8日。对符合条件的研究,由2位研究者按照纳入和排除标准,独立筛选文献、提取资料、评价文献质量,并交叉核对后,采用Stata 12.0版软件进行Meta分析。结果共纳入25篇文献,包括25个研究(n=11 199);结果显示,与安慰药比较,达格列净导致泌尿生殖系统感染的风险较高(P<0.05);服用达格列净的女性患者较男性患者发生泌尿生殖系统感染的风险高(P<0.05)。结论 2型糖尿病患者服用达格列净治疗时,应定期监测尿常规和检查生殖系统,若发生尿路感染或生殖系统感染时尽量换用其他药物治疗,避免感染加重。
Objective To evaluate the correlation between the dapagliflozin and urinary tract and genital infection in patients with type 2 diabetes mellitus( T2DM) and provide reference for clinical safe use. Methods Randomized,placebocontrolled,double-blinded clinical trials reported the association between dapagliflozin and urinary tract or genital infection were collected in electronic databases,including PubMed,EMbase,the Cochrane Library and Clinical Trials until January 8th 2018.Two authors assessed,extracted and crosschecked data according to the literature inclusion and exclusion criteria independently.Data were analyzed by Stata 12. 0. Results Twenty-five clinical trials( n = 11 199) were included. Comparing to placebo group,the risk of urinary tract infection and genital infection were significant higher( P<0.05). Besides,the incidence rate was higher in female patients than male patients( P < 0. 05). Conclusion The patients with T2DM who received dapagliflozin should regularly monitor urine routine and reproductive system. If urinary tract infection or genital infection occurred,T2DM patients should switch to other medications to avoid severe infections.
Objective To evaluate the correlation between the dapagliflozin and urinary tract and genital infection in patients with type 2 diabetes mellitus( T2DM) and provide reference for clinical safe use. Methods Randomized,placebocontrolled,double-blinded clinical trials reported the association between dapagliflozin and urinary tract or genital infection were collected in electronic databases,including PubMed,EMbase,the Cochrane Library and Clinical Trials until January 8th 2018.Two authors assessed,extracted and crosschecked data according to the literature inclusion and exclusion criteria independently.Data were analyzed by Stata 12. 0. Results Twenty-five clinical trials( n = 11 199) were included. Comparing to placebo group,the risk of urinary tract infection and genital infection were significant higher( P<0.05). Besides,the incidence rate was higher in female patients than male patients( P < 0. 05). Conclusion The patients with T2DM who received dapagliflozin should regularly monitor urine routine and reproductive system. If urinary tract infection or genital infection occurred,T2DM patients should switch to other medications to avoid severe infections.
引文
[1]IDRIS I,DONNELLY R.Sodium-glucose co-transporter-2inhibitors:an emerging new class of oral antidiabetic drug[J].Diab Obesity Metabol,2009,11(2):79-88.
[2]MEROVCI A,SOLIS-HERRERA C,DANIELE G,et al.Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production[J].J Clin Invest,2014,124(2):509-514.
[3]BOYKO E J,FIHN S D,SCHOLES D,et al.Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women[J].Am JEpidemiol,2005,161(6):557-564.
[4]DONDERS G G.Lower genital tract infections in diabetic women[J].Curr Infect Dis Rep,2002,4(6):536-539.
[5]NAUCK M A,DEL PRATO S,MEIER J J,et al.Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin:A randomized,52-week,double-blind,activecontrolled noninferiority trial[J].Diabetes Care,2011,34(9):2015-2022.
[6]WEBER M A,MANSFIELD T A,ALESSI F,et al.Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade[J].Blood Press,2016,25(2):93-103.
[7]WILDING J P H,NORWOOD P,T'JOEN C,et al.A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers:applicability of a novel insulin-independent treatment[J].Diabetes Care,2009,32(9):1656-1662.
[8]YANG W,HAN P,MIN K W,et al.Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure:A randomized controlled trial[J].JDiabetes,2016,8(6):796-808.
[9]WILDING J P H,WOO V,ROHWEDDER K,et al.Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin:Efficacy and safety over 2 years[J].Diab Obesity Metabol,2014,16(2):124-136.
[10]WEBER M A,MANSFIELD T A,CAIN V A,et al.Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy:A randomised,double-blind,placebo-controlled,phase 3 study[J].Lancet Diabet Endocrinol,2016,4(3):211-220.
[11]STROJEK K,YOON K H,HRUBA V,et al.Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus sustains glycemic control and weight loss over 48weeks:A randomized,double-blind,parallel-group,placebocontrolled trial[J].Diabetes Ther,2014,5(1):267-283.
[12]SCHUMM-DRAEGER P M,BURGESS L,KORANYI L,et al.Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes:A 16-week randomized,placebocontrolled clinical trial[J].Diab Obesity Metabol,2015,17(1):42-51.
[13]ROSENSTOCK J,VICO M,WEI L,et al.Effects of dapagliflozin,an SGLT2 inhibitor,on Hb A1c,body weight,and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy[J].Diabetes Care,2012,35(7):1473-1478.
[14]MUDALIAR S,HENRY R R,BODEN G,et al.Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin[J].Diabet Technol Therapeut,2014,16(3):137-144.
[15]MATTHAEI S,BOWERING K,ROHWEDDER K,et al.Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea:A24-week randomized,double-blind clinical trial[J].Diabetes Care,2015,38(3):365-372.
[16]MATHIEU C,RANETTI A E,LI D,et al.Randomized,double-blind,phase 3 trial of triple therapy with dapagliflozin add-on to saxagliptin plus metformin in type 2diabetes[J].Diabetes Care,2015,38(11):2009-2017.
[17]LIST J F,WOO V,MORALES E,et al.Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes[J].Diabetes Care,2009,32(4):650-657.
[18]LEITER L A,CEFALU W T,DE BRUIN T W A,et al.Dapagliflozin added to usual care in individuals with type 2diabetes mellitus with preexisting cardiovascular disease:A24-week,multicenter,randomized,double-blind,placebocontrolled study with a 28-week extension[J].J Am Geriatr Soc,2014,62(7):1252-1262.
[19]LAMBERS HEERSPINK H J,DE ZEEUW D,WIE L,et al.Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes[J].Diabet Obesity Metabol,2013,15(9):853-862.
[20]KOHAN D E,FIORETTO P,TANG W,et al.Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control[J].Kidney International,2014,85(4):962-971.
[21]KAKU K,KIYOSUE A,INOUE S,et al.Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type2 diabetes inadequately controlled by diet and exercise[J].Diabet Obesity Metabol,2014,16(11):1102-1110.
[22]KAKU K,INOUE S,MATSUOKA O,et al.Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control:A phase II multicentre,randomized,double-blind,placebo-controlled trial[J].Diabet Obesity Metabol,2013,15(5):432-440.
[23]JI L,MA J,LI H,et al.Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus:a randomized,blinded,prospective phase III study[J].Clin Ther,2014,36(1):84-100.
[24]JABBOUR S A,HARDY E,SUGG J,et al.Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin:A 24-week,multicenter,randomized,doubleblind,placebo-controlled study[J].Diabetes Care,2014,37(3):740-750.
[25]CEFALU W T,LEITER L A,DE BRUIN T W,et al.Dapagliflozin's effects on glycemia and cardiovascular risk factors in high-risk patients with type 2 diabetes:A 24-week,multicenter,randomized,double-blind,placebocontrolled study with a 28-week extension[J].Diabetes Care,2015,38(7):1218-1227.
[26]BOLINDER J,LJUNGGREN O,JOHANSSON L,et al.Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2diabetes mellitus inadequately controlled on metformin[J].Diabetes Obes Metab,2014,16(2):159-169.
[27]BAILEY C J,MORALES VILLEGAS E C,WOO V,et al.Efficacy and safety of dapagliflozin monotherapy in people with type 2 diabetes:A randomized double-blind placebocontrolled 102-week trial[J].Diabetic Med,2015,32(4):531-541.
[28]BAILEY C J,IQBAL N,T'JOEN C,et al.Dapagliflozin monotherapy in drug-na6ve patients with diabetes:Arandomized-controlled trial of low-dose range[J].Diabet Obesity Metabol,2012,14(10):951-959.
[29]BAILEY C J,GROSS J L,HENNICKEN D,et al.Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin:A randomized,double-blind,placebo-controlled 102-week trial[J].BMC Med,2013,11:43.
[30]GEERLING S E,STOLK R P,CAMPS M J,et al.Asymptomatic bacteriuria may be considered a complication in women with diabetes.Diabetes Mellitus Women Asymptomatic Bacteriuria Utrecht Study Group.[J].Diabetes Care,2000,23(6):744-749.
[31]GEERLINGS S E.Urinary tract infections in patients with diabetes mellitus:epidemiology,pathogenesis and treatment[J].Int J Antimicrob Agents,2008,31(Suppl 1):S54-57.
[32]GHOSH R K,GHOSH S M,CHAWLA S,et al.SGLT2inhibitors:a new emerging therapeutic class in the treatment of type 2 diabetes mellitus[J].J Clin Pharmacol,2012,52(4):457-463.
[33]GEERLINGS S E,STOLK R P,CAMPS M J,et al.Risk factors for symptomatic urinary tract infection in women with diabetes[J].Diabetes Care,2000,23(12):1737-1741.
[34]JOHNSSON K M,PTASZYNSKA A,SCHMITZ B,et al.Urinary tract infections in patients with diabetes treated with dapagliflozin[J].J Diabetes Complications,2013,27(5):473-478.
[35]BALASOIU D,VAN KESSEL K C,VAN KATS-RENAUDH J,et al.Granulocyte function in women with diabetes and asymptomatic bacteriuria[J].Diabetes Care,1997,20(3):392-395.
[36]FOXMAN B.Epidemiology of urinary tract infections:incidence,morbidity,and economic costs[J].Am J Med,2002,113(Suppl 1A):5S-13S.
[37]RAZ R.Asymptomatic bacteriuria--clinical significance and management[J].Nephrol Dial Transplant,2001,16(Suppl6):135-136.
[2]MEROVCI A,SOLIS-HERRERA C,DANIELE G,et al.Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production[J].J Clin Invest,2014,124(2):509-514.
[3]BOYKO E J,FIHN S D,SCHOLES D,et al.Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women[J].Am JEpidemiol,2005,161(6):557-564.
[4]DONDERS G G.Lower genital tract infections in diabetic women[J].Curr Infect Dis Rep,2002,4(6):536-539.
[5]NAUCK M A,DEL PRATO S,MEIER J J,et al.Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin:A randomized,52-week,double-blind,activecontrolled noninferiority trial[J].Diabetes Care,2011,34(9):2015-2022.
[6]WEBER M A,MANSFIELD T A,ALESSI F,et al.Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade[J].Blood Press,2016,25(2):93-103.
[7]WILDING J P H,NORWOOD P,T'JOEN C,et al.A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers:applicability of a novel insulin-independent treatment[J].Diabetes Care,2009,32(9):1656-1662.
[8]YANG W,HAN P,MIN K W,et al.Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure:A randomized controlled trial[J].JDiabetes,2016,8(6):796-808.
[9]WILDING J P H,WOO V,ROHWEDDER K,et al.Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin:Efficacy and safety over 2 years[J].Diab Obesity Metabol,2014,16(2):124-136.
[10]WEBER M A,MANSFIELD T A,CAIN V A,et al.Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy:A randomised,double-blind,placebo-controlled,phase 3 study[J].Lancet Diabet Endocrinol,2016,4(3):211-220.
[11]STROJEK K,YOON K H,HRUBA V,et al.Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus sustains glycemic control and weight loss over 48weeks:A randomized,double-blind,parallel-group,placebocontrolled trial[J].Diabetes Ther,2014,5(1):267-283.
[12]SCHUMM-DRAEGER P M,BURGESS L,KORANYI L,et al.Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes:A 16-week randomized,placebocontrolled clinical trial[J].Diab Obesity Metabol,2015,17(1):42-51.
[13]ROSENSTOCK J,VICO M,WEI L,et al.Effects of dapagliflozin,an SGLT2 inhibitor,on Hb A1c,body weight,and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy[J].Diabetes Care,2012,35(7):1473-1478.
[14]MUDALIAR S,HENRY R R,BODEN G,et al.Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin[J].Diabet Technol Therapeut,2014,16(3):137-144.
[15]MATTHAEI S,BOWERING K,ROHWEDDER K,et al.Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea:A24-week randomized,double-blind clinical trial[J].Diabetes Care,2015,38(3):365-372.
[16]MATHIEU C,RANETTI A E,LI D,et al.Randomized,double-blind,phase 3 trial of triple therapy with dapagliflozin add-on to saxagliptin plus metformin in type 2diabetes[J].Diabetes Care,2015,38(11):2009-2017.
[17]LIST J F,WOO V,MORALES E,et al.Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes[J].Diabetes Care,2009,32(4):650-657.
[18]LEITER L A,CEFALU W T,DE BRUIN T W A,et al.Dapagliflozin added to usual care in individuals with type 2diabetes mellitus with preexisting cardiovascular disease:A24-week,multicenter,randomized,double-blind,placebocontrolled study with a 28-week extension[J].J Am Geriatr Soc,2014,62(7):1252-1262.
[19]LAMBERS HEERSPINK H J,DE ZEEUW D,WIE L,et al.Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes[J].Diabet Obesity Metabol,2013,15(9):853-862.
[20]KOHAN D E,FIORETTO P,TANG W,et al.Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control[J].Kidney International,2014,85(4):962-971.
[21]KAKU K,KIYOSUE A,INOUE S,et al.Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type2 diabetes inadequately controlled by diet and exercise[J].Diabet Obesity Metabol,2014,16(11):1102-1110.
[22]KAKU K,INOUE S,MATSUOKA O,et al.Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control:A phase II multicentre,randomized,double-blind,placebo-controlled trial[J].Diabet Obesity Metabol,2013,15(5):432-440.
[23]JI L,MA J,LI H,et al.Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus:a randomized,blinded,prospective phase III study[J].Clin Ther,2014,36(1):84-100.
[24]JABBOUR S A,HARDY E,SUGG J,et al.Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin:A 24-week,multicenter,randomized,doubleblind,placebo-controlled study[J].Diabetes Care,2014,37(3):740-750.
[25]CEFALU W T,LEITER L A,DE BRUIN T W,et al.Dapagliflozin's effects on glycemia and cardiovascular risk factors in high-risk patients with type 2 diabetes:A 24-week,multicenter,randomized,double-blind,placebocontrolled study with a 28-week extension[J].Diabetes Care,2015,38(7):1218-1227.
[26]BOLINDER J,LJUNGGREN O,JOHANSSON L,et al.Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2diabetes mellitus inadequately controlled on metformin[J].Diabetes Obes Metab,2014,16(2):159-169.
[27]BAILEY C J,MORALES VILLEGAS E C,WOO V,et al.Efficacy and safety of dapagliflozin monotherapy in people with type 2 diabetes:A randomized double-blind placebocontrolled 102-week trial[J].Diabetic Med,2015,32(4):531-541.
[28]BAILEY C J,IQBAL N,T'JOEN C,et al.Dapagliflozin monotherapy in drug-na6ve patients with diabetes:Arandomized-controlled trial of low-dose range[J].Diabet Obesity Metabol,2012,14(10):951-959.
[29]BAILEY C J,GROSS J L,HENNICKEN D,et al.Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin:A randomized,double-blind,placebo-controlled 102-week trial[J].BMC Med,2013,11:43.
[30]GEERLING S E,STOLK R P,CAMPS M J,et al.Asymptomatic bacteriuria may be considered a complication in women with diabetes.Diabetes Mellitus Women Asymptomatic Bacteriuria Utrecht Study Group.[J].Diabetes Care,2000,23(6):744-749.
[31]GEERLINGS S E.Urinary tract infections in patients with diabetes mellitus:epidemiology,pathogenesis and treatment[J].Int J Antimicrob Agents,2008,31(Suppl 1):S54-57.
[32]GHOSH R K,GHOSH S M,CHAWLA S,et al.SGLT2inhibitors:a new emerging therapeutic class in the treatment of type 2 diabetes mellitus[J].J Clin Pharmacol,2012,52(4):457-463.
[33]GEERLINGS S E,STOLK R P,CAMPS M J,et al.Risk factors for symptomatic urinary tract infection in women with diabetes[J].Diabetes Care,2000,23(12):1737-1741.
[34]JOHNSSON K M,PTASZYNSKA A,SCHMITZ B,et al.Urinary tract infections in patients with diabetes treated with dapagliflozin[J].J Diabetes Complications,2013,27(5):473-478.
[35]BALASOIU D,VAN KESSEL K C,VAN KATS-RENAUDH J,et al.Granulocyte function in women with diabetes and asymptomatic bacteriuria[J].Diabetes Care,1997,20(3):392-395.
[36]FOXMAN B.Epidemiology of urinary tract infections:incidence,morbidity,and economic costs[J].Am J Med,2002,113(Suppl 1A):5S-13S.
[37]RAZ R.Asymptomatic bacteriuria--clinical significance and management[J].Nephrol Dial Transplant,2001,16(Suppl6):135-136.