TY - JOUR
T1 - Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease
T2 - A systematic review and meta-analysis
AU - Toyama, Tadashi
AU - Neuen, Brendon L.
AU - Jun, Min
AU - Ohkuma, Toshiaki
AU - Neal, Bruce
AU - Jardine, Meg J.
AU - Heerspink, Hiddo L.
AU - Wong, Muh Geot
AU - Ninomiya, Toshiharu
AU - Wada, Takashi
AU - Perkovic, Vlado
N1 - Funding Information:
This work was not specifically funded but it was supported in part by programme grant funding provided by the National Health and Medical Research Council of Australia, which had no role in study design, data collection, data analysis, data interpretation or writing of the report.
Funding Information:
B. L. N. has received travel support from Janssen and is funded by a John Chalmers PhD Scholarship from The George Institute for Global Health, a University Postgraduate Award from UNSW Sydney and a Clarendon Scholarship from the University of Oxford. T. T. is supported by the Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers. T. O. is supported by a John Chalmers Postdoctoral Fellowship from The George Institute for Global Health. M. J. is supported by a Scientia Fellowship from UNSW Sydney, Australia. M. J. J. is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Career Development Fellowship; is responsible for research projects that have received unrestricted funding from Gambro, Baxter, CSL, Amgen, Eli Lilly and Merck; has served on advisory boards sponsored by Akebia, Baxter and Boehringer Ingelheim; has spoken at scientific meetings sponsored by Janssen, Amgen and Roche, with any consultancy, honoraria or travel support paid to her institution. M. G. W. has received honorarium for scientific lectures from AstraZeneca, Amgen and Baxter, and is supported by a Diabetes Australia Research Trust Millennium Grant. B. N. has received research support from the Australian National Health and Medical Research Council Principal Research Fellowship and from Janssen, Roche, Servier, and Merck Schering Plough; and is serving on advisory boards and/or has involvement in CME programs for Abbott, Janssen, Novartis, Pfizer, Roche and Servier, with any consultancy, honoraria, or travel support paid to his institution. H. J. L. H. has served as a consultant for Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Fresenius, Janssen and Merck; and has received grant support from AstraZeneca and Boehringer Ingelheim, with all honoraria paid to his institution. T. W. is a national lead investigator of a renal outcome study of a sodium-glucose cotransporter-2 (SGLT2) inhibitor (canagliflozin). V. P. is receiving research support from the Australian National Health and Medical Research Council (Senior Research Fellowship and Program Grant); is serving on Steering Committees for AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen and Pfizer; and is serving on advisory boards and/or speaking at scientific meetings for AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Roche, Sanofi, Servier and Vitae, with all honoraria paid to his employer. M. J. J., H. L. H., B. N. and V. P. are members of the steering committee of a renal outcome study of a sodium-glucose cotransporter-2 (SGLT2) inhibitor (canagliflozin), with V. P. serving as chair of the steering committee. The George Institute for Global Health, which funds B. L. N. and T. O., provides contract research services to Janssen for trials of SGLT2 inhibitors. The other authors report no declarations of interest.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/5
Y1 - 2019/5
N2 - Aim: The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results: Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (−0.29%; 95% CI, −0.39 to −0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70-0.94) and heart failure (RR, 0.61; 95% CI, 0.48-0.78), without a clear effect on all-cause mortality (HR, 0.86; 95% CI, 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m2/y; 95% CI, 0.78-1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion: Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.
AB - Aim: The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results: Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (−0.29%; 95% CI, −0.39 to −0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70-0.94) and heart failure (RR, 0.61; 95% CI, 0.48-0.78), without a clear effect on all-cause mortality (HR, 0.86; 95% CI, 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m2/y; 95% CI, 0.78-1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion: Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.
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U2 - 10.1111/dom.13648
DO - 10.1111/dom.13648
M3 - Article
C2 - 30697905
AN - SCOPUS:85062363657
SN - 1462-8902
VL - 21
SP - 1237
EP - 1250
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 5
ER -
