2 replies to this topic

[Sillewater]

Diabetes Care. 2000 Oct;23(10):1539-44.


Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.
Hamada Y, Nakamura J, Naruse K, Komori T, Kato K, Kasuya Y, Nagai R, Horiuchi S, Hotta N.

Third Department of Internal Medicine, Nagoya University School of Medicine, Japan. yhama@med.nagoya-u.ac.jp


Abstract
OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress.

RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography

RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients.

CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.

Did a search of the forum and found nothing on this drug? Anyone know anything about it?

[Sillewater]

J Diabetes Complications. 2010 Nov-Dec;24(6):424-32. Epub 2009 Aug 27.


Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N(ɛ)-carboxymethyl lysine.
Kawai T, Takei I, Tokui M, Funae O, Miyamoto K, Tabata M, Hirata T, Saruta T, Shimada A, Itoh H.

Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. tkawai@sc.itc.keio.ac.jp


Abstract
OBJECTIVE: We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes.

METHODS: A total of 38 type 2 diabetic patients (22 men and 16 women; mean ± S.E.M. age 63.3 ± 1.0 years; duration of diabetes 9.6 ± 0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N(ɛ)-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean ± S.E.M. duration of diabetes 8.2 ± 0.7 years) as control (C group).

RESULTS: The EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (-0.18 ± 0.13 mU/ml in the EP group vs. +0.22 ± 0.09 mU/ml in the C group, P<.05) after 1 year.

CONCLUSIONS: Epalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs.

J Diabetes Complications. 2010 Sep-Oct;24(5):354-60. Epub 2009 Sep 11.


Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review.
Schemmel KE, Padiyara RS, D'Souza JJ.

Mercy Medical Center, Dubuque, IA 52001, USA.


Abstract
PURPOSE: The purpose of this article was to examine how aldose reductase (AR) inhibitors are used in the prevention and treatment of peripheral neuropathy in diabetes, specifically focusing on efficacy.

METHODS: Medline searches were used to identify clinical trials investigating AR inhibitors and their proposed mechanism of action, efficacy, and adverse effects. Additionally, the references of the articles returned by the Medline search were examined for pertinent publications.

RESULTS: Three AR inhibitors were selected for review. Modest improvements in the preservation and restoration of nerve conduction velocities were reported in the studies. Additionally, patients reported improvements in the subjective symptoms associated with diabetic peripheral neuropathy. Adverse effects for the studied agents were minimal or not reported.

CONCLUSIONS: Given the mechanism by which diabetic peripheral neuropathy can result, targeting the polyol pathway as a method of treatment appears promising, yet the efficacy of newer AR inhibitors is still to be proven. Currently, these agents are not marketed in the United States. As newer studies emerge, diabetes educators will learn more about their efficacy and safety in preventing and treating diabetic peripheral neuropathy.

Int J Diabetes Dev Ctries. 2009 Jan;29(1):28-34.


Efficacy, safety, and tolerability of Epalrestat compared to Methylcobalamine in patients with diabetic neuropathy.
Maladkar M, Rajadhyaksha G, Venkataswamy N, Hariharan RS, Lohati SR.

Aristo Pharmaceuticals P Ltd Mumbai-53, India.


Abstract
OBJECTIVE: To compare the efficacy, safety, and tolerability of Epalrestat with Methylcobalamine in patients with diabetic neuropathy.

MATERIALS AND METHODS: This prospective, open-labeled, comparative, and multicentric study was conducted on an outpatient basis by qualified investigators at four different centers. A total of 242 patients with diabetic neuropathy were enrolled in the study. The enrollment of patients was as per inclusion/exclusion criteria. After obtaining their informed consent, they were individually interviewed, examined, investigated, and treated as per the study protocol. Each patient was administered with one tablet containing Epalrestat 50 mg thrice daily or Methylcobalamine 500 microg thrice daily for 12 weeks. They were followed up at the end of weeks 4, 8, and 12 for their examination. Therapeutic success was assessed in terms of clinical symptoms, physical examinations, and electrophysiological assessments.

RESULTS: A significant improvement in all the efficacy parameters was observed with Epalrestat treatment compared to Methylcobalamin treatment. The efficacy parameters assessed were loss of sensation, burning sensation, numbness, muscle cramps, spontaneous pain, weakness, mean score of isometric muscle strength, tendon reflexes, and sensation. Epalrestat treatment is associated with very few adverse events. The tolerability to Epalrestat treatment was also reported to be excellent in the majority of the study population compared to tolerability to Methylcobalamine. Patients as well as physicians reported that the Epalrestat treatment is superior in efficacy and safety parameters compared to Methylcobalamin.

CONCLUSION: The present study concludes that Epalrestat has better efficacy and safety profile than Methylcobalamine in the treatment of diabetic neuropathy.

PMID: 20062561 [PubMed - in process]PMCID: PMC2802362

I'm curious if anyone knows of diabetic patients taking this drug. I haven't heard of it.

[YOLF]

http://care.diabetes...ntent/29/7/1538

 

RESULTS—Over the 3-year period, epalrestat prevented the deterioration of median MNCV, MFWL, and VPT seen in the control group. The between-group difference in change from baseline in median MNCV was 1.6 m/s (P< 0.001). Although a benefit with epalrestat was observed in cardiovascular autonomic nerve function variables, this did not reach statistical significance compared with the control group. Numbness of limbs, sensory abnormality, and cramping improved significantly with epalrestat versus the control group. The effects of epalrestat on median MNCV were most evident in subjects with better glycemic control and with no or mild microangiopathies.

CONCLUSIONS—Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy.

 

Safe and effective, though while for some parameters it wasn't significant, it might be different for otherwise healthy individuals as those with the best glycemic control saw the best results. Perhaps it could prevent or reduce the risk of diabetes?