Fibrates are effective in raising HDL cholesterol levels in individuals with type 2 diabetes and in improving LDL cholesterol quality. Two recent large studies have examined the effect of fenofibrate on renal outcomes in individuals with type 2 diabetes. The efficacy of this drug class has not been tested in individuals with renal impairment. There is also an increased potential for side-effects in this subgroup. A subgroup analysis of the Diabetes Atherosclerosis Intervention Study (DAIS), examined the effects of fenofibrate treatment (vs placebo) in 314 people with type 2 diabetes (Canada and Selleckchem PD98059 Europe) with mild to moderate lipid abnormalities and normo to microalbuminuria.113 The study
length was a minimum of 3 years. Regression of albuminuria (defined as micro to normoalbuminuria or macro to microalbuminuria) was significantly higher in the treatment group (13%) compared with the placebo group (11%), while progression of albuminuria was significantly lower in the treatment group (8%) compared with the placebo group (18%). Significantly more people showed no change in albuminuria in the treatment group (79%) compared with the placebo group (71%). The use of ACEi and ARBs increased during the course of the study; however, the
use at the end of the trial was not significantly different between the groups at the end of the trial. The differences between groups in the progression and regression of albuminuria remained significant after controlling for baseline BP and HbA1c. The high throughput screening compounds final urinary albumin was significantly correlated with either HbA1c Adenosine triphosphate level or BP. A significant correlation was observed between urinary albumin and baseline fasting triglyceride
(TG) levels. After fenofibrate treatment urinary albumin levels correlated significantly with HDL-C levels but not with changes in TG. The study was not able to assess the persistence of the reduction to microalbuminuria after cessation of treatment. Keech et al.114 and Radermecker & Scheen115 report the large (9795) multinational Fenofibrate Intervention and event Lowering in Diabetes (FIELD) study, which included assessment of progression and regression of albuminuria. Fenofibrate was associated with a significantly lower progression and significantly higher regression of albuminuria, however, the overall differences were relatively small (in the order of 2%). Albuminuria was a secondary outcome of the study. In the only study to compare statins and fibrates, head to head, in 71 individuals with type 2 diabetes both benzafibrate and pravastatin prevented increase in the urinary albumin excretion rate over 4 years, with no difference observed between drug classes.116 A number of other agents have clinically useful effects on dyslipidaemia in individuals with type 2 diabetes, including probucol and glitazones.