Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria

TLDR

Urinary albumin excretion frequently persists in diabetic patients on ACEI/ARB therapy, and sulodexide—a mixture of heparan and dermatan sulfate—has been proposed to reduce this persistent albuminuria. The study aimed to evaluate the effect of six months of sulodexide therapy on urinary albumin excretion in type 2 diabetic patients with persistent albuminuria. In a multi‑center, double‑blind, randomized pilot, 149 patients with ACR 20–300 mg/g were assigned to placebo, 200 mg, or 400 mg sulodexide for six months, with the primary endpoint being normoalbuminuria or a ≥50 % ACR reduction. Sulodexide achieved the primary endpoint in 25.3 % of patients versus 15.4 % of placebo (P = 0.26), with 33.3 % in the 200 mg group and 18.4 % in the 400 mg group, indicating a non‑significant trend toward benefit.

Abstract

Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial.A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization.The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed.Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.