Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

From the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (S.-M.J., M.-K.L.); Diabetes Center, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea (K.A.H.); Department of Internal Medicine, Gangnam Sacred Heart Hospital, Hallym Medical University, Seoul, Korea (J.M.Y.); Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul (T.S.S.); Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (S.H.C.); Department of Internal Medicine, Yonsei University Wonju College of Medicine, Korea (C.H.C.); Department of Internal Medicine, Gachon University, Incheon, Korea (I.B.P.); Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea (E.J.R.); Department of Internal Medicine, Korea University, Seoul (S.H.B.); Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea (T.S.P.); Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea (I.-K.L.); Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea (S.-H.K.); Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea (Y.-C.H.); Department of Internal Medicine, Severance Hospital, Yonsei University of Collage of Medicine, Seoul, Korea (B.S.C.); Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea (H.W.L.); and Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea (M.-S.N.). From the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (S.-M.J., M.-K.L.); Diabetes Center, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea (K.A.H.); Department of Internal Medicine, Gangnam Sacred Heart Hospital, Hallym Medical University, Seoul, Korea (J.M.Y.); Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul (T.S.S.); Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (S.H.C.); Department of Internal Medicine, Yonsei University Wonju College of Medicine, Korea (C.H.C.); Department of Internal Medicine, Gachon University, Incheon, Korea (I.B.P.); Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea (E.J.R.); Department of Internal Medicine, Korea University, Seoul (S.H.B.); Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea (T.S.P.); Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea (I.-K.L.); Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea (S.-H.K.); Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea (Y.-C.H.); Department of Internal Medicine, Severance Hospital, Yonsei University of Collage of Medicine, Seoul, Korea (B.S.C.); Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea (H.W.L.); and Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea (M.-S.N.). leemk@skku.edu.

Arteriosclerosis, thrombosis, and vascular biology. 2016;(10):2108-14

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 months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.

Methodological quality

Metadata