Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis

Tadashi Toyama, Brendon L. Neuen, Min Jun, Toshiaki Ohkuma, Bruce Neal, Meg J. Jardine, Hiddo L. Heerspink, Muh Geot Wong, Toshiharu Ninomiya, Takashi Wada, Vlado Perkovic

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1237-1250
Number of pages14
JournalDiabetes, Obesity and Metabolism
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Sodium-Glucose Transporter 2
Symporters
Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Meta-Analysis
Kidney
Safety
Glycosylated Hemoglobin A
Glomerular Filtration Rate
Albuminuria
MEDLINE
Libraries
Randomized Controlled Trials
Heart Failure
Biomarkers
Stroke
Myocardial Infarction
Placebos
Body Weight
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease : A systematic review and meta-analysis. / Toyama, Tadashi; Neuen, Brendon L.; Jun, Min; Ohkuma, Toshiaki; Neal, Bruce; Jardine, Meg J.; Heerspink, Hiddo L.; Wong, Muh Geot; Ninomiya, Toshiharu; Wada, Takashi; Perkovic, Vlado.

In: Diabetes, Obesity and Metabolism, Vol. 21, No. 5, 01.05.2019, p. 1237-1250.

Research output: Contribution to journalArticle

Toyama, Tadashi ; Neuen, Brendon L. ; Jun, Min ; Ohkuma, Toshiaki ; Neal, Bruce ; Jardine, Meg J. ; Heerspink, Hiddo L. ; Wong, Muh Geot ; Ninomiya, Toshiharu ; Wada, Takashi ; Perkovic, Vlado. / Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease : A systematic review and meta-analysis. In: Diabetes, Obesity and Metabolism. 2019 ; Vol. 21, No. 5. pp. 1237-1250.
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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

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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

PY - 2019/5/1

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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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