Actos Now for the prevention of diabetes (ACT NOW) study

BACKGROUND: Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS(®)) can prevent progression of IGT to type...

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Autores principales: DeFronzo, Ralph A, Banerji, MaryAnn, Bray, George A, Buchanan, Thomas A, Clement, Stephen, Henry, Robert R, Kitabchi, Abbas E, Mudaliar, Sunder, Musi, Nicolas, Ratner, Robert, Reaven, Peter D, Schwenke, Dawn, Stentz, Frankie B, Tripathy, Devjit
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725044/
https://www.ncbi.nlm.nih.gov/pubmed/19640291
http://dx.doi.org/10.1186/1472-6823-9-17
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author DeFronzo, Ralph A
Banerji, MaryAnn
Bray, George A
Buchanan, Thomas A
Clement, Stephen
Henry, Robert R
Kitabchi, Abbas E
Mudaliar, Sunder
Musi, Nicolas
Ratner, Robert
Reaven, Peter D
Schwenke, Dawn
Stentz, Frankie B
Tripathy, Devjit
author_facet DeFronzo, Ralph A
Banerji, MaryAnn
Bray, George A
Buchanan, Thomas A
Clement, Stephen
Henry, Robert R
Kitabchi, Abbas E
Mudaliar, Sunder
Musi, Nicolas
Ratner, Robert
Reaven, Peter D
Schwenke, Dawn
Stentz, Frankie B
Tripathy, Devjit
author_sort DeFronzo, Ralph A
collection PubMed
description BACKGROUND: Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS(®)) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial. METHODS/DESIGN: 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA(1C), lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance. CONCLUSION: ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM. TRIAL REGISTRATION: clinical trials.gov identifier: NCT00220961
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spelling pubmed-27250442009-08-12 Actos Now for the prevention of diabetes (ACT NOW) study DeFronzo, Ralph A Banerji, MaryAnn Bray, George A Buchanan, Thomas A Clement, Stephen Henry, Robert R Kitabchi, Abbas E Mudaliar, Sunder Musi, Nicolas Ratner, Robert Reaven, Peter D Schwenke, Dawn Stentz, Frankie B Tripathy, Devjit BMC Endocr Disord Study Protocol BACKGROUND: Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS(®)) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial. METHODS/DESIGN: 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA(1C), lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance. CONCLUSION: ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM. TRIAL REGISTRATION: clinical trials.gov identifier: NCT00220961 BioMed Central 2009-07-29 /pmc/articles/PMC2725044/ /pubmed/19640291 http://dx.doi.org/10.1186/1472-6823-9-17 Text en Copyright © 2009 DeFronzo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Study Protocol
DeFronzo, Ralph A
Banerji, MaryAnn
Bray, George A
Buchanan, Thomas A
Clement, Stephen
Henry, Robert R
Kitabchi, Abbas E
Mudaliar, Sunder
Musi, Nicolas
Ratner, Robert
Reaven, Peter D
Schwenke, Dawn
Stentz, Frankie B
Tripathy, Devjit
Actos Now for the prevention of diabetes (ACT NOW) study
title Actos Now for the prevention of diabetes (ACT NOW) study
title_full Actos Now for the prevention of diabetes (ACT NOW) study
title_fullStr Actos Now for the prevention of diabetes (ACT NOW) study
title_full_unstemmed Actos Now for the prevention of diabetes (ACT NOW) study
title_short Actos Now for the prevention of diabetes (ACT NOW) study
title_sort actos now for the prevention of diabetes (act now) study
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725044/
https://www.ncbi.nlm.nih.gov/pubmed/19640291
http://dx.doi.org/10.1186/1472-6823-9-17
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