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

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.

The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through ‘stacking’ of drugs from different classes

“…Pentoxifylline is another drug which, through tumour necrosis factor‐α suppression, has been shown to decrease macroalbuminuria (but not microalbuminuria) and to decelerate the decline in renal function 49 …”

Combine and Conquer: With Type 2 Diabetes Polypharmacy Is Essential Not Only to Achieve Glycemic Control but Also to Treat the Comorbidities and Stabilize or Slow the Advancement of Diabetic Nephropathy

“…Another therapy that is a candidate to reduce albuminuria and frequency of renal decompensation is pentoxifylline [ 64 ]. This older drug through TNF α suppression has been shown to decrease macroalbuminuria, but not microalbuminuria, and decelerate the progression to renal failure in patients with diabetic nephropathy.…”

Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients

“…Pentoxifylline in combination with tocopherol is described as "PENTO protocol" for the management of osteoradionecrosis with beneficial antioxidant and antifibrotic properties [17]. Currently, these drugs are considered as having a positive synergistic therapeutic efficacy in treating chronic ischemic pathological conditions, such as diabetic microangiopathy, osteoradionecrosis, MRONJ, and osteomyelitis; however, the evidence is still limited and the mechanism of action remains unclear [17,18,[21][22][23][24][25].…”