pentoxifylline and Insulin Resistance studies

Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.

Research Excerpts

Excerpt	Relevance	Reference
"We have previously shown that pentoxifylline (PTX) protects from vascular complications associated with insulin resistance (IR)."	7.80	Pentoxifylline alleviates cardiac ischemia and dysfunction following experimental angina in insulin resistance. ( Azhar, A; El-Bassossy, HM, 2014)
"Cardiac inflammation was interrogated via expression levels of TNF α, interleukins 6 and 10, phosphorylated STAT4 and lipoxygenases 12 and 12/15."	5.62	Lisofylline mitigates cardiac inflammation in a mouse model of obesity through improving insulin secretion and activating cardiac AMPK signaling pathway. ( Abdelzaher, LA; Ali, M; Bakr, MH; Desai, AA; Mali, V; Radwan, E; Sayed, SA, 2021)
"Pentoxifylline (PTX) is a well-tolerated drug used to treat vascular insufficiency."	5.37	Pentoxifylline alleviates vascular impairment in insulin resistance via TNF-α inhibition. ( El-Bassossy, HM; El-Moselhy, MA; Mahmoud, MF, 2011)
" Therapy with PTX resulted in significant decreases in 9-HODE and 13-oxoODE, oxidized lipid products of linoleic acid (LA) linked to histological severity in nonalcoholic fatty liver disease."	5.16	Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. ( Feldstein, AE; Fu, X; Hazen, SL; Kirwan, JP; Lopez, R; McCullough, AJ; Yerian, LM; Zein, CO, 2012)
"Pentoxifylline significantly alleviated hepatic lipid accumulation, reduced blood lipid levels and improved insulin resistance."	4.12	Pentoxifylline attenuates nonalcoholic fatty liver by inhibiting hepatic macrophage polarization to the M1 phenotype. ( Feng, Y; Liu, H; Ping, J; Wen, X; Xu, D; Zhao, W, 2022)
"We have previously shown that pentoxifylline (PTX) protects from vascular complications associated with insulin resistance (IR)."	3.80	Pentoxifylline alleviates cardiac ischemia and dysfunction following experimental angina in insulin resistance. ( Azhar, A; El-Bassossy, HM, 2014)
"Cardiac inflammation was interrogated via expression levels of TNF α, interleukins 6 and 10, phosphorylated STAT4 and lipoxygenases 12 and 12/15."	1.62	Lisofylline mitigates cardiac inflammation in a mouse model of obesity through improving insulin secretion and activating cardiac AMPK signaling pathway. ( Abdelzaher, LA; Ali, M; Bakr, MH; Desai, AA; Mali, V; Radwan, E; Sayed, SA, 2021)
"Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease linked to insulin resistance, oxidative stress, and cytokine imbalance."	1.56	Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats. ( Abdel-Latif, RG; El-Deen, RM; Heeba, GH; Khalifa, MMA, 2020)
"Pentoxifylline (PTX) is a well-tolerated drug used to treat vascular insufficiency."	1.37	Pentoxifylline alleviates vascular impairment in insulin resistance via TNF-α inhibition. ( El-Bassossy, HM; El-Moselhy, MA; Mahmoud, MF, 2011)

Research

Studies (12)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (8.33)	29.6817
2010's	8 (66.67)	24.3611
2020's	3 (25.00)	2.80

Authors	Studies
Xu, D	1
Zhao, W	1
Feng, Y	1
Wen, X	1
Liu, H	1
Ping, J	1
El-Deen, RM	1
Heeba, GH	1
Abdel-Latif, RG	1
Khalifa, MMA	1
Ali, M	1
Bakr, MH	1
Abdelzaher, LA	1
Sayed, SA	1
Mali, V	1
Desai, AA	1
Radwan, E	1
Mehanna, OM	1
El Askary, A	1
Al-Shehri, S	1
El-Esawy, B	1
Azhar, A	1
El-Bassossy, HM	2
Metwally, AH	1
Ganesh, S	1
Rustgi, VK	1
Zaitone, S	1
Hassan, N	1
El-Orabi, N	1
El-Awady, el-S	1
Zein, CO	2
Yerian, LM	2
Gogate, P	1
Lopez, R	2
Kirwan, JP	2
Feldstein, AE	2
McCullough, AJ	2
El-Moselhy, MA	1
Mahmoud, MF	1
Fu, X	1
Hazen, SL	1
Fan, JG	1
Qian, Y	1
Zheng, XY	1
Cai, XB	1
Lu, YS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial[NCT00590161]	Phase 2	55 participants (Actual)	Interventional	2006-12-31	Completed
A Phase II Trial of Pentoxifylline in Newly-Diagnosed Biliary Atresia[NCT01774487]	Phase 2	17 participants (Actual)	Interventional	2013-02-04	Terminated (stopped due to Target enrollment was not reached because the medication, pentoxifylline, has a taste that is not well tolerated by infants. The study team decided to end the study before meeting the enrollment goal because of the medication taste.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The NAFLD Activity Score (NAS) grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and balloning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2). (NCT00590161)
Timeframe: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)

Alanine Amino Transferase (ALT) Levels at 2 Years of Life

Intervention	NAS score units (Mean)
Pentoxifylline 400 mg PO Tid	-1.6
Placebo Tid	-0.1

The investigators will record the ALT levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Scale 14-45 U/L, with a higher level indicating a worse outcome. (NCT01774487)
Timeframe: 2 years of age

Number of Participants Achieving Zero or Positive Weight Z-scores 12 Weeks After Starting PTX Therapy

Intervention	U/L (Mean)
Pentoxifylline - Group 1	160

The investigators will track the weight of patients over the course of therapy in patients receiving 90 days of PTX (this is recorded as part of routine clinical care). The weight will then be compared to standards to calculate a z-score. Normal weight Z-score is greater than or equal to 0, with a higher number of patients meeting this indicating a better outcome. (NCT01774487)
Timeframe: 12 weeks after starting therapy

Number of Participants With Normal Serum Conjugated Bilirubin Levels 12 Weeks After Starting PTX (Pentoxifylline) Therapy

Intervention	Participants (Count of Participants)
Pentoxifylline - Group 1	0
Group 2	0

The investigators will track the serum conjugated bilirubin (CB) levels over the course of therapy in patients receiving 90 days of PTX (this laboratory test is drawn as part of routine care). Normal CB is 0.0-0.3 mg/dL, with a higher number of patients meeting this indicating a better outcome. (NCT01774487)
Timeframe: 12 weeks after starting therapy

Platelet Levels at 2 Years of Life

Intervention	Participants (Count of Participants)
Pentoxifylline - Group 1	6
Pentoxifylline - Group 2	0

The investigators will record platelet levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Scale 189-403*10^3 Platelets/μL, with a lower level indicating a worse outcome. (NCT01774487)
Timeframe: 2 years of age

Spleen Size at 2 Years of Age

Intervention	10^3 Platelets/μL (Mean)
Pentoxifylline - Group 1	208

"The investigators will measure spleen size by ultrasound at 2 years of age, in patients who had received PTX therapy earlier and still have their native liver. Normal spleen size range (10th-90th percentile) at this age is 6.4-8.6 cm, with a value exceeding this range indicating a worse outcome." (NCT01774487)
Timeframe: 2 years of age

Time to Liver Transplant

Intervention	cm (Mean)
Pentoxifylline - Group 1	10.0

The investigators will track time to liver transplant. The shorter time to liver transplant indicates a worse outcome. (NCT01774487)
Timeframe: Baseline and up to two years after therapy finishes

Article	Year
Pentoxifylline attenuates nonalcoholic fatty liver by inhibiting hepatic macrophage polarization to the M1 phenotype. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2022, Volume: 106 Topics: Animals; Cholesterol; Eosine Yellowish-(YS); Glucose; Insulin Resistance; Insulins; Lipopolysacchari	2022
Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats. Fundamental & clinical pharmacology, 2020, Volume: 34, Issue:3 Topics: Animals; Antioxidants; Biomarkers; Cilostazol; Diet, High-Fat; Fatty Liver; Inflammation; Insulin; I	2020
Lisofylline mitigates cardiac inflammation in a mouse model of obesity through improving insulin secretion and activating cardiac AMPK signaling pathway. Cytokine, 2021, Volume: 138 Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Apoptosis; Blood Glucose; Body Weight; Disea	2021
Effect of phosphodiesterase inhibitors on renal functions and oxidant/antioxidant parameters in streptozocin-induced diabetic rats. Archives of physiology and biochemistry, 2018, Volume: 124, Issue:5 Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Hyperglycemia; Hypog	2018
Pentoxifylline alleviates cardiac ischemia and dysfunction following experimental angina in insulin resistance. PloS one, 2014, Volume: 9, Issue:5 Topics: Adiponectin; Administration, Oral; Angina Pectoris; Animals; Diet; Disease Models, Animal; Electroca	2014
Pentoxifylline in the management of metabolic syndrome and chronic hepatitis C. Medical hypotheses, 2014, Volume: 83, Issue:6 Topics: Antiviral Agents; Cardiovascular Diseases; Hepatitis C, Chronic; Humans; Insulin Resistance; Liver C	2014
Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease. European journal of pharmacology, 2011, Jul-15, Volume: 662, Issue:1-3 Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; Body Weight; C	2011
Pentoxifylline alleviates vascular impairment in insulin resistance via TNF-α inhibition. Naunyn-Schmiedeberg's archives of pharmacology, 2011, Volume: 384, Issue:3 Topics: Animals; Aorta, Thoracic; Blood Glucose; Chemotaxis, Leukocyte; Connective Tissue; Endothelial Cells	2011
[Effects of pentoxifylline on hepatic nuclear factor-kappa B signaling pathway and insulin resistance in nonalcoholic steatohepatitis rats induced by fat-rich diet]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2006, Volume: 14, Issue:10 Topics: Animals; Fatty Liver; Glucose Transporter Type 2; I-kappa B Proteins; Insulin Receptor Substrate Pro	2006

pentoxifylline and Insulin Resistance