Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis

被引:401
作者
Zaccardi, F. [1 ,2 ]
Webb, D. R. [1 ,2 ]
Htike, Z. Z. [1 ,2 ]
Youssef, D. [1 ,2 ]
Khunti, K. [1 ,2 ]
Davies, M. J. [1 ,2 ]
机构
[1] Univ Leicester, Diabet Res Ctr, Leicester LE5 4PW, Leics, England
[2] UHL NHS Trust, Leicester Diabet Ctr, Diabet Res Ctr, Leicester, Leics, England
关键词
canagliflozin; dapagliflozin; empagliflozin; meta-analysis; review; SGLT2; inhibitor; systematic; ADD-ON THERAPY; METFORMIN PLUS SULFONYLUREA; DOUBLE-BLIND; GLYCEMIC CONTROL; JAPANESE PATIENTS; DAPAGLIFLOZIN MONOTHERAPY; EMPAGLIFLOZIN MONOTHERAPY; BACKGROUND METFORMIN; PARALLEL-GROUP; WEIGHT-LOSS;
D O I
10.1111/dom.12670
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aim: To assess the comparative efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors in adults with type 2 diabetes. Methods: We electronically searched randomized controlled trials (>= 24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta-analyses. Results: A total of 38 trials (23 997 participants) were included. Compared with placebo, all SGLT2 inhibitors reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and blood pressure, and slightly increased HDL cholesterol. Canagliflozin 300 mg reduced HbA1c, FPG and systolic blood pressure and increased LDL cholesterol to a greater extent compared with other inhibitors at any dose. At their highest doses, canagliflozin 300 mg reduced: HbA1c by 0.2% [95% confidence interval (CI) 0.1-0.3] versus both dapagliflozin 10 mg and empagliflozin 25 mg; FPG by 0.6 mmol/l (95% CI 0.3-0.9) and 0.5 mmol/l (95% CI 0.1-0.8) versus dapagliflozin and empagliflozin, respectively; and systolic blood pressure by 2 mmHg (95% CI 1.0-3.0) versus dapagliflozin; and increased LDL cholesterol by 0.13 mmol/l (95% CI 0.03-0.23) and 0.15 mmol/l (95% CI 0.06-0.23) versus dapagliflozin and empagliflozin, respectively. The highest doses of inhibitors had similar effects on body weight reduction. Canagliflozin 300 and 100 mg increased the risk of hypoglycaemia versus placebo, dapagliflozin 10 mg and empagliflozin 10 mg [odds ratios (ORs) 1.4-1.6]. Dapagliflozin 10 mg increased the risk of urinary tract infection versus placebo and empagliflozin 25 mg (ORs 1.4). All inhibitors similarly increased the risk of genital infection (ORs 4-6 versus placebo). Conclusions: Although they increase the risk of genital infection, SGLT2 inhibitors are effective in improving cardiometabolic markers in type 2 diabetes, with canagliflozin 300 mg performing better in this respect than other inhibitors. Further studieswill clarifywhether these differences are likely to translate into differing long-term outcomes.
引用
收藏
页码:783 / 794
页数:12
相关论文
共 69 条
[1]   Lowering plasma glucose concentration by inhibiting renal sodium-glucose cotransport [J].
Abdul-Ghani, M. A. ;
DeFronzo, R. A. .
JOURNAL OF INTERNAL MEDICINE, 2014, 276 (04) :352-363
[2]  
[Anonymous], VALUE HLTH
[3]   Long-term treatment with empagliflozin as add-on to oral antidiabetes therapy in Japanese patients with type 2 diabetes mellitus [J].
Araki, E. ;
Tanizawa, Y. ;
Tanaka, Y. ;
Taniguchi, A. ;
Koiwai, K. ;
Kim, G. ;
Salsali, A. ;
Woerle, H. J. ;
Broedl, U. C. .
DIABETES OBESITY & METABOLISM, 2015, 17 (07) :665-674
[4]   Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial [J].
Bailey, C. J. ;
Villegas, E. C. Morales ;
Woo, V. ;
Tang, W. ;
Ptaszynska, A. ;
List, J. F. .
DIABETIC MEDICINE, 2015, 32 (04) :531-541
[5]   Dapagliflozin monotherapy in drug-naive patients with diabetes: a randomized-controlled trial of low-dose range [J].
Bailey, C. J. ;
Iqbal, N. ;
T'joen, C. ;
List, J. F. .
DIABETES OBESITY & METABOLISM, 2012, 14 (10) :951-959
[6]   Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial [J].
Bailey, Clifford J. ;
Gross, Jorge L. ;
Hennicken, Delphine ;
Iqbal, Nayyar ;
Mansfield, Traci A. ;
List, James F. .
BMC MEDICINE, 2013, 11
[7]   Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes [J].
Bode, B. ;
Stenlof, K. ;
Harris, S. ;
Sullivan, D. ;
Fung, A. ;
Usiskin, K. ;
Meininger, G. .
DIABETES OBESITY & METABOLISM, 2015, 17 (03) :294-303
[8]   Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin [J].
Bolinder, J. ;
Ljunggren, O. ;
Johansson, L. ;
Wilding, J. ;
Langkilde, A. M. ;
Sjostrom, C. D. ;
Sugg, J. ;
Parikh, S. .
DIABETES OBESITY & METABOLISM, 2014, 16 (02) :159-169
[9]   Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension [J].
Cefalu, William T. ;
Leiter, Lawrence A. ;
de Bruin, Tjerk W. A. ;
Gause-Nilsson, Ingrid ;
Sugg, Jennifer ;
Parikh, Shamik J. .
DIABETES CARE, 2015, 38 (07) :1218-1227
[10]   Graphical Tools for Network Meta-Analysis in STATA [J].
Chaimani, Anna ;
Higgins, Julian P. T. ;
Mavridis, Dimitris ;
Spyridonos, Panagiota ;
Salanti, Georgia .
PLOS ONE, 2013, 8 (10)