Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin–Angiotensin System Blockade

Abstract

Objective-To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Approach and Results-This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was −7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. Conclusions-Four

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

“…Accurately monitoring early decreases in GFR is especially important in patients with diabetes because of their increased risk for kidney damage. Thus, several clinical trials use cystatin C as a secondary biomarker for renal function in diabetic populations …”

NADPH oxidase inhibitor development for diabetic nephropathy through water tank model

“…Many studies have demonstrated that oxidative stress plays an important role in DN. Therefore, various clinical trials for therapeutic agents regulating oxidative stress are continuously being conducted (Table 1) [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89]. Although no effective therapy exists for treatment of DN, clinical trials for therapeutic Nox inhibitors are ongoing [88,89].…”

Highlighting Diabetes Mellitus

“…These authors reported that although probucol treatment resulted in significantly lowered total cholesterol and low density lipoprotein (LDL) cholesterol levels, no reduction in urinary albumin excretion was observed. However, it is to be noted that the majority of the subjects were already on statin therapy 55 .…”