Glycemic Control and Effects of Canagliflozin in Reducing Albuminuria and eGFR: A Post Hoc Analysis of the CREDENCE Trial.

Publisher: Wolters Kluwer Health Country of Publication: United States NLM ID: 101271570 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-905X (Electronic) Linking ISSN: 15559041 NLM ISO Abbreviation: Clin J Am Soc Nephrol Subsets: MEDLINE

Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health
Original Publication: Washington, D.C. : American Society of Nephrology, c2005-

Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Diabetic Nephropathies*/drug therapy ; Diabetic Nephropathies*/etiology ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/diagnosis ; Renal Insufficiency, Chronic*/drug therapy; Adult ; Humans ; Canagliflozin/adverse effects ; Glycated Hemoglobin ; Albuminuria/drug therapy ; Albuminuria/etiology ; Creatinine ; Glycemic Control/adverse effects ; Albumins ; Glomerular Filtration Rate

Background: In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin improved kidney and cardiovascular outcomes and reduced the rate of estimated glomerular filtration decline (eGFR slope) in patients with type 2 diabetes and CKD. In other clinical trials of patients with CKD or heart failure, the protective effects of SGLT2 inhibitors on eGFR slope were greater in participants with versus participants without type 2 diabetes. This post hoc analysis of the CREDENCE trial assessed whether the effects of canagliflozin on eGFR slope varied according to patient subgroups by baseline glycated hemoglobin A1c (HbA1c).
Methods: CREDENCE ( ClinicalTrials.gov [ NCT02065791 ]) was a randomized controlled trial in adults with type 2 diabetes with an HbA1c of 6.5%-12.0%, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urinary albumin-to-creatinine ratio of 300-5000 mg/g. Participants were randomly assigned to canagliflozin 100 mg once daily or placebo. We studied the effect of canagliflozin on eGFR slope using linear mixed-effects models.
Results: The annual difference in total eGFR slope was 1.52 ml/min per 1.73 m 2 (95% confidence interval [CI], 1.11 to 1.93) slower in participants randomized to canagliflozin compared with placebo. The rate of eGFR decline was faster in those with poorer baseline glycemic control. The mean difference in total eGFR slope between canagliflozin and placebo was greater in participants with poorer baseline glycemic control (difference in eGFR slope of 0.39, 1.36, 2.60, 1.63 ml/min per 1.73 m 2 for HbA1c subgroups 6.5%-7.0%, 7.0%-8.0%, 8.0%-10.0%, 10.0%-12.0%, respectively; Pinteraction = 0.010). The mean difference in change from baseline in urinary albumin-to-creatinine ratio between participants randomized to canagliflozin and placebo was smaller in patients with baseline HbA1c 6.5%-7.0% (-17% [95% CI, -28 to -5]) compared with those with an HbA1c of 7.0%-12% (-32% [95% CI, -40 to -28]; Pinteraction = 0.03).
Conclusions: The effect of canagliflozin on eGFR slope in patients with type 2 diabetes and CKD was more pronounced in patients with higher baseline HbA1c, partly because of the more rapid decline in kidney function in these individuals.
Clinical Trial Registry Name and Registration Number: Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), NCT02065791.
(Copyright © 2023 by the American Society of Nephrology.)

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ClinicalTrials.gov NCT02065791

0SAC974Z85 (Canagliflozin)
0 (Glycated Hemoglobin)
AYI8EX34EU (Creatinine)
0 (Albumins)

Date Created: 20230331 Date Completed: 20230612 Latest Revision: 20240603

20240603

PMC10278833

10.2215/CJN.0000000000000161

36999981