Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study.
OBJECTIVE
Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2)) 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.


METHODS
Type 2 diabetic patients (aged 50-75 years) with eGFR ≥30 mL/min/1.73 m(2) 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 m(2)). 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 m(2): 0.68 [0.47-0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m(2): 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.
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. rudee.ting@ctc.usyd.edu.au
Ru-Dee
RD
Ting
Anthony C
AC
Keech
Paul L
PL
Drury
Mark W
MW
Donoghoe
John
J
Hedley
Alicia J
AJ
Jenkins
Timothy M E
TM
Davis
Seppo
S
Lehto
David
D
Celermajer
R John
RJ
Simes
Kushwin
K
Rajamani
Kim
K
Stanton
D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects* / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged
D000960:Hypolipidemic Agents; D011345:Fenofibrate