Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis

Abstract

Introduction: Micro-and macrovascular complications of diabetes are leading morbidities in the world population. They are responsible not only for increased mortality but also severe disabilities, which jeopardize quality of life (e.g., blindness, walking limitations, and renal failure requiring dialysis). The new antidiabetic agents (e.g., glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter inhibitors) are increasingly recognized as breakthrough agents in the treatment of diabetes and prevention of diabetic complications.

Vasoprotective Effect of Sulodexide in Diabetic Retinopathy

“…These complications include conditions such as blindness, limitations in mobility and renal failure necessitating dialysis. The pervasive impact of these complications underscores the urgent need for effective strategies in diabetes management to mitigate their occurrence and reduce associated health burdens [27]. As per literature reports and conducted studies, the vasoprotective effect of sulodexide is harnessed in the treatment and prevention of vascular complications associated with diabetes.…”

“…In recent years, a large meta-analysis by Bignamini et al [32] analyzed 45 studies with 2,817 participants monitoring any effect of sulodexide in subjects with diabetes, in relation to renal, vascular, and ocular complication. The findings from this meta-analysis suggest that Sulodexide has a positive impact on ocular diseases and may reduce the severity of diabetic retinopathy.…”

“…In the context of diabetic nephropathy, it's essential to recognize that glycosaminoglycans play a dual role as crucial components of both the endothelial glycocalyx and the glomerular basement membrane [46]. The versatile benefits of sulodexide in individuals with renal complications of diabetes extend to inhibiting inflammatory reactions and mitigating oxidative stress [47,48].…”

“…The previously mentioned meta-analysis [27] also analyzed articles on diabetic nephropathy. Analysis of studies presenting data on the effect of sulodexide in the treatment of diabetic nephropathy, especially monitored as urinary albumin excretion, showed a significant reduction in albuminuria compared to control groups.…”

The Glomerular Endothelium Restricts Albumin Filtration

“…As EC glycocalyx glypican-1 is required to elicit shear-induced NO synthesis (184,186), it seems likely that glycocalyx degradation is, in fact, the proximate cause of reduced flow-dependent NO synthesis in generalized EC dysfunction. In experimental diabetes, endomucin restored the EC glycocalyx (221,271), and in human diabetic patients partial restoration of the EC glycocalyx with sulodexide, an orally administered mixture of GAGs, not only lowers blood pressure, but also reduces albuminuria and other diabetic complications (272)(273)(274)(275)(276). Hence, microalbuminuria reflects the endothelial barrier defect that accompanies glycocalyx disruption and EC dysfunction in cardiovascular disease, diabetes and chronic kidney disease.…”