Benefits and Safety of Long-Term Fenofibrate Therapy in People With Type 2 Diabetes and Renal Impairment

The FIELD Study

  1. on behalf of the FIELD Study Investigators*
  1. 1National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
  2. 2Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  3. 3Auckland Diabetes Centre, Auckland, New Zealand
  4. 4Department of Internal Medicine, Wairau Hospital, Blenheim, New Zealand
  5. 5Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  6. 6School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
  7. 7Department of Medicine, Kuopio University Hospital, Kuopio, Finland
  8. 8Department of Endocrinology and Diabetes, Royal Perth Hospital, Perth, Western Australia, Australia
  1. Corresponding authors: Ru-Dee Ting, rudee.ting{at}ctc.usyd.edu.au, and Anthony C. Keech, tony{at}ctc.usyd.edu.au.

Abstract

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat.

RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment.

CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.

Footnotes

  • R.-D.T. and A.C.K. are joint first authors.

  • Clinical trial reg. no. ISRCTN64783481, www.isrctn.org.

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1109/-/DC1.

  • * A complete list of members of the FIELD Study can be found in the Supplementary Data online.

  • The study sponsors had no role in the data collection or analysis. Both the authors and the study management committee had final responsibility for the decision to submit the article for publication.

  • Received August 2, 2011.
  • Accepted November 2, 2011.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

| Table of Contents

This Article

  1. Diabetes Care vol. 35 no. 2 218-225
  1. Supplementary Data
  2. All Versions of this Article:
    1. dc11-1109v1
    2. 35/2/218 most recent