SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis

  • Samuel Seidu
    Correspondence
    Corresponding author at: Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK.
    Affiliations
    Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK

    Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK
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  • Setor K. Kunutsor
    Affiliations
    Translational Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Learning and Research Building (Level 1) Bristol, UK

    National Institute of Health Research, Bristol Biomedical Research Centre, University of Bristol, Bristol, UK
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  • Xavier Cos
    Affiliations
    Barcelona Ciutat Research Support Unit-IDIAP Jordo Gol, redlAPP, Barcelona, Spain
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  • Syed Gillani
    Affiliations
    University of Wolverhampton, Diabetes Centre, New Cross Hospital, Wednesfield Road, Wolverhampton, WV10 0QP, UK
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  • Kamlesh Khunti
    Affiliations
    Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK

    Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK
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  • For and on behalf of Primary Care Diabetes Europe
Published:February 23, 2018DOI:https://doi.org/10.1016/j.pcd.2018.02.001

      Highlights

      • SGLT2 inhibition is associated with a transient decrease in eGFR.
      • SGLT2 inhibition prevents deterioration of renal function and death from kidney disease.
      • In populations with renal impairment, SGLT2-Is are associated with preservation of renal function.
      • SGLT2-Is are associated with improvement in UACR in populations with renal impairment.

      Abstract

      Background

      Sodium–glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60 ml/min/1.73 m2 and/or UACR > 300 and ≤5000 mg/g] by conducting a systematic review and meta-analysis of available studies.

      Methods

      Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled.

      Results

      42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51 ml/min/1.73 m2; 95% CI: −0.69, 1.72; p = 403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease.

      Conclusions

      Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2 inhibition prevents further renal function deterioration and death from kidney disease in these patients.

      Keywords

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