Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Oxford University Press
      Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-
    • Subject Terms:
      Benzhydryl Compounds/*therapeutic use ; Diabetes Mellitus, Type 2/*drug therapy ; Glucosides/*therapeutic use ; Hypoglycemic Agents/*therapeutic use ; Renal Insufficiency, Chronic/*complications ; Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use; Adult ; Aged ; Albuminuria/chemically induced ; Benzhydryl Compounds/adverse effects ; Blood Pressure/drug effects ; Body Weight/drug effects ; Creatinine/urine ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Female ; Glomerular Filtration Rate/drug effects ; Glucosides/adverse effects ; Glycated Hemoglobin/metabolism ; Humans ; Hypoglycemic Agents/adverse effects ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects
    • Abstract:
      Background: The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD).
      Methods: In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45 mL/min/1.73 m2 receiving placebo (n = 69) or dapagliflozin 5 or 10 mg (n = 151). Effects on UACR were determined in a subgroup of patients with baseline UACR ≥30 mg/g (n = 136).
      Results: Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10 mg were 0.03% [95% confidence interval (CI) -0.3-0.3] and 0.03% (95% CI -0.2-0.3) during the overall 102-week period. Dapagliflozin 5 and 10 mg compared with placebo reduced UACR by - 47.1% (95% CI -64.8 to - 20.6) and -38.4% (95% CI -57.6 to - 10.3), respectively. Additionally, dapagliflozin 5 and 10 mg compared with placebo reduced BP and body weight. eGFR increased with placebo during the first 4 weeks but did not change with dapagliflozin. There were no between-group differences in eGFR at the end of follow-up. Adverse events associated with renal function occurred more frequently in the dapagliflozin 10-mg group. These events were mainly asymptomatic increases in serum creatinine.
      Conclusions: Dapagliflozin did not decrease HbA1c in patients with type 2 diabetes and Stages 3b-4 CKD, but decreased UACR, BP and body weight to a clinically meaningful extent. These results support a large outcome trial in this population to confirm long-term safety and efficacy in reducing adverse clinical endpoints.
    • Comments:
      Erratum in: Nephrol Dial Transplant. 2018 Jul 1;33(7):1280. (PMID: 29762740)
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    • Accession Number:
      0 (Benzhydryl Compounds)
      0 (Glucosides)
      0 (Glycated Hemoglobin A)
      0 (Hypoglycemic Agents)
      0 (Sodium-Glucose Transporter 2 Inhibitors)
      1ULL0QJ8UC (dapagliflozin)
      AYI8EX34EU (Creatinine)
    • Publication Date:
      Date Created: 20180126 Date Completed: 20191009 Latest Revision: 20221207
    • Publication Date:
      20240628
    • Accession Number:
      PMC6212718
    • Accession Number:
      10.1093/ndt/gfx350
    • Accession Number:
      29370424