Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes: a prospective randomized double-blind multicenter study

Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Sheen, Seung Soo; Chung, Choon Hee; Ahn, Chul Woo; Kim, Se Hwa; Cho, Yong Wook; Park, Seok Won; Kim, Soo‐Kyung; Kim, Chul Sik; Kim, Kyung Wook; Lee, Kwan Woo

doi:10.1186/s13098-015-0060-1

Cited by 29 publications

(27 citation statements)

References 41 publications

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“…88 A reduction in proteinuria (23%) relative to that seen in the placebo group (4%) was statistically significant ( p=0.012). In addition, modest improvements in fasting blood glucose (−10 mg/dL), glycated haemoglobin (−0.34) and homeostatic model assessment of insulin resistance (HOMA-IR) (−0.79) were seen in the pentoxifylline group that were significantly different relative to the small increases in these parameters observed in the placebo group.…”

Section: Improved Diabetic Controlmentioning

confidence: 86%

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Pentoxifylline for vascular health: a brief review of the literature

2016

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Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes—some of them attributable to pentoxifylline metabolites—appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable.

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Section: Improved Diabetic Controlmentioning

confidence: 86%

“…A very recent randomised controlled trial evaluated pentoxifylline (400 mg three times a day) in patients with type 2 diabetes over 6 months 88. A reduction in proteinuria (23%) relative to that seen in the placebo group (4%) was statistically significant (p=0.012).…”

Section: Pentoxifylline: Myriad Potential Benefits For Vascular Healthmentioning

confidence: 99%

Pentoxifylline for vascular health: a brief review of the literature

2016

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“…128 129 A Korean multicenter RCT evaluated the effect of pentoxifylline 1200 mg/day or placebo in 174 patients with diabetic nephropathy who had albuminuria (>30 mg/g creatinine) while taking an ACE inhibitor or ARB for six months. 130 Proteinuria decreased significantly in the pentoxifylline group (23% v 4%; P=0.012), but no difference was seen in estimated GFR between the groups. An older and smaller Mexican RCT had evaluated the same dose for a longer duration (12 months) in 37 patients, 20 with early and 17 with moderate diabetic nephropathy.…”

Section: Pentoxifyllinementioning

confidence: 84%

How to prevent the microvascular complications of type 2 diabetes beyond glucose control

Valencia

Flórez

2017

BMJ

160

109

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“…Second, the mechanisms by which PTX exerts antiproteolytic effects on skeletal muscles remain unknown. Finally, PTX has been strongly suggested for use in managing various complications related to diabetes mellitus, including diabetic nephropathy (8), foot ulcers due to diabetic neuropathy (48), and insulin resistance (30). Thus, understanding the benefits of PTX for sparing skeletal muscles could contribute to evidence supporting the repositioning of this drug for treating one more diabetic complication, as well as to attenuate the loss of muscle mass occurring in other catabolic conditions.…”

Section: Discussionmentioning

confidence: 99%

Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of pentoxifylline on skeletal muscles of diabetic rats

Arcaro

Assis

Zanon

et al. 2018

Journal of Applied Physiology

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Advances in the knowledge of the mechanisms controlling protein breakdown in skeletal muscles have allowed the exploration of new options for treating muscle-wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE) inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly via inhibiting protein breakdown. The aim of this study was to explore the mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of atrogin-1 and muscle RING finger-1 were decreased, as were the activities of caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX, which at least partly explains the drop in the ubiquitin conjugate (EDL) levels and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE activity and increased cAMP content in muscles of diabetic rats; moreover, it also increased both the protein levels of exchange protein directly activated by cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle mass was practically prevented in diabetic rats treated with PTX. These findings advance our understanding of the mechanisms underlying the antiproteolytic effects of PTX and suggest the use of PDE inhibitors as a strategy to activate cAMP signaling, which is emerging as a promising target for treating muscle mass loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in addition to βAR agonists, phosphodiesterase inhibitors such as pentoxifylline (PTX) can be an interesting option. This study advances the understanding of the mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of diabetic rats, which involve the activation of both exchange protein directly activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and calpain/caspase-3-proteolytic machinery.

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Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes: a prospective randomized double-blind multicenter study

Cited by 29 publications

References 41 publications

Pentoxifylline for vascular health: a brief review of the literature

Pentoxifylline for vascular health: a brief review of the literature

How to prevent the microvascular complications of type 2 diabetes beyond glucose control

Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of pentoxifylline on skeletal muscles of diabetic rats

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