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Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer

It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones (mTOT), thereby avoiding peroxisome proliferator–activated receptor-γ (PPAR-γ)-dependent side effects. In this phase IIb clinical trial, 258 patients with type 2 diabetes comp...

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Autores principales: Colca, J R, VanderLugt, J T, Adams, W J, Shashlo, A, McDonald, W G, Liang, J, Zhou, R, Orloff, D G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604641/
https://www.ncbi.nlm.nih.gov/pubmed/23462886
http://dx.doi.org/10.1038/clpt.2013.10
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author Colca, J R
VanderLugt, J T
Adams, W J
Shashlo, A
McDonald, W G
Liang, J
Zhou, R
Orloff, D G
author_facet Colca, J R
VanderLugt, J T
Adams, W J
Shashlo, A
McDonald, W G
Liang, J
Zhou, R
Orloff, D G
author_sort Colca, J R
collection PubMed
description It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones (mTOT), thereby avoiding peroxisome proliferator–activated receptor-γ (PPAR-γ)-dependent side effects. In this phase IIb clinical trial, 258 patients with type 2 diabetes completed a 12-week protocol with 50, 100, or 150 mg of MSDC-0160 (an mTOT modulator), 45 mg pioglitazone HCl (a PPAR-γ agonist), or a placebo. The two active treatments lowered fasting glucose levels to the same extent. The decreases in glycated hemoglobin (HbA(1c)) observed with the two higher doses of MSDC-0160 were not different from those associated with pioglitazone. By contrast, fluid retention as evidenced by reduction in hematocrit, red blood cells, and total hemoglobin was 50% less in the MSDC-0160–treated groups. There was also a smaller increase in high-molecular-weight (HMW) adiponectin with MSDC-0160 than with pioglitazone (P < 0.0001), suggesting that MSDC-0160 produces less expansion of white adipose tissue. Thus, mTOT modulators may have glucose-lowering effects similar to those of pioglitazone but without the adverse effects associated with PPAR-γ agonists.
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spelling pubmed-36046412013-04-01 Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer Colca, J R VanderLugt, J T Adams, W J Shashlo, A McDonald, W G Liang, J Zhou, R Orloff, D G Clin Pharmacol Ther Articles It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones (mTOT), thereby avoiding peroxisome proliferator–activated receptor-γ (PPAR-γ)-dependent side effects. In this phase IIb clinical trial, 258 patients with type 2 diabetes completed a 12-week protocol with 50, 100, or 150 mg of MSDC-0160 (an mTOT modulator), 45 mg pioglitazone HCl (a PPAR-γ agonist), or a placebo. The two active treatments lowered fasting glucose levels to the same extent. The decreases in glycated hemoglobin (HbA(1c)) observed with the two higher doses of MSDC-0160 were not different from those associated with pioglitazone. By contrast, fluid retention as evidenced by reduction in hematocrit, red blood cells, and total hemoglobin was 50% less in the MSDC-0160–treated groups. There was also a smaller increase in high-molecular-weight (HMW) adiponectin with MSDC-0160 than with pioglitazone (P < 0.0001), suggesting that MSDC-0160 produces less expansion of white adipose tissue. Thus, mTOT modulators may have glucose-lowering effects similar to those of pioglitazone but without the adverse effects associated with PPAR-γ agonists. Nature Publishing Group 2013-04 2013-03-06 /pmc/articles/PMC3604641/ /pubmed/23462886 http://dx.doi.org/10.1038/clpt.2013.10 Text en Copyright © 2013 American Society of Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Articles
Colca, J R
VanderLugt, J T
Adams, W J
Shashlo, A
McDonald, W G
Liang, J
Zhou, R
Orloff, D G
Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title_full Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title_fullStr Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title_full_unstemmed Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title_short Clinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
title_sort clinical proof-of-concept study with msdc-0160, a prototype mtot-modulating insulin sensitizer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604641/
https://www.ncbi.nlm.nih.gov/pubmed/23462886
http://dx.doi.org/10.1038/clpt.2013.10
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