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10-13-2021 | Complications | Adis Journal Club | Article

Diabetes Therapy

Are the Protean Effects of Pentoxifylline in the Therapy of Diabetes and Its Complications Still Relevant?

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Authors: David S. H. Bell

Abstract 

Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.

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Key Summary Points

Pentoxifylline’s effects on diabetic complications are not modulated through improved rheolitic effect; rather it is mediated through its anti-inflammatory, anti-proliferative and anti-fibrotic effects, which occur through activation of the protein kinase system and inhibition of tumor necrosis factor-alpha (TNF-α) and other leukotrienes

Pentoxifylline has the potential to improve microvascular diabetic complications (particularly nephropathy)

Macrovascular complications such as multi-infarct dementia, transient ischemic attacks and heart failure may also benefit from pentoxifylline therapy

Due to improved endogenous insulin release, glycemic control may be improved with pentoxifylline

Insulin resistance is lowered with pentoxifylline as is hepatic steatosis, inflammation and perhaps fibrosis in non-alcoholic steatohepatitis

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