Article

Diabetologia

, Volume 54, Issue 2, pp 280-290

First online:

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

  • T. M. E. DavisAffiliated withSchool of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia
  • , R. TingAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials CentreRoyal Prince Alfred Hospital Email author 
  • , J. D. BestAffiliated withDepartment of Medicine, St Vincent’s Hospital, University of Melbourne
  • , M. W. DonoghoeAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials Centre
  • , P. L. DruryAffiliated withAuckland Diabetes Centre, Greenlane Clinical Centre
  • , D. R. SullivanAffiliated withRoyal Prince Alfred Hospital
  • , A. J. JenkinsAffiliated withDepartment of Medicine, St Vincent’s Hospital, University of Melbourne
  • , R. L. O’ConnellAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials Centre
  • , M. J. WhitingAffiliated withFlinders Medical Centre
    • , P. P. GlasziouAffiliated withCentre for Evidence-Based Medicine, University of Oxford
    • , R. J. SimesAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials Centre
    • , Y. A. KesäniemiAffiliated withInstitute of Clinical Medicine, Department of Internal Medicine, University of OuluBiocenter Oulu, University of OuluClinical Research Centre, Oulu University Hospital
    • , V. J. GebskiAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials Centre
    • , R. S. ScottAffiliated withLipid & Diabetes Research Group, Christchurch Hospital
    • , A. C. KeechAffiliated withThe FIELD Study, c/o NHMRC Clinical Trials CentreRoyal Prince Alfred Hospital Email author 
    • , on behalf of the FIELD Study investigators

Abstract

Aims/hypothesis

Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate’s renal effects overall and in a FIELD washout sub-study.

Methods

Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat.

Results

During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min−1 1.73 m−2 annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min−1 1.73 m−2, p = 0.065) than on placebo (6.9 ml min−1 1.73 m−2, p < 0.001), sparing 5.0 ml min−1 1.73 m−2 (95% CI 2.3–7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9–18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48).

Conclusions/interpretation

Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited.

Trial registration

ISRCTN64783481

Funding

The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia

Keywords

Albuminuria Creatinine Diabetes Fenofibrate FIELD GFR Nephropathy Renal impairment