@article{6278e3ee4ec2476fb8e22c740731c3e6,
title = "Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW",
abstract = "Context: Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear. Objective: To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW. Design, Settings and Patients: Two-hundred ninety-three subjects (placebo [PLAC], n = 138; PIO, n = 152) completed a median followup of 11.7 mo after study medication was stopped. Results: Diabetes developed in 138 (12.3%) of PLAC vs 17 of 152 PIO patients (11.2%; P = not significant, PIO vs PLAC). However, the cumulative incidence of diabetes from start of study medication to end of washout period remained significantly lower in PIO vs PLAC (10.7 vs 22.3%; P = .005). After therapy was discontinued, 23.0% (35/152) of PIO-treated patients remained normal-glucose tolerant (NGT) vs 13.8% (19/138) of PLAC-treated patients (P = .04). Insulin secretion/insulin resistance index (I0-120 /G0-120 × Matsuda index) was markedly lower in subjects with impaired glucose tolerance (IGT) who converted to diabetes during followup vs those who remained IGT or NGT. The decline in-cell function (insulin secretion/insulin resistance index) was similar in subjects with IGT who developed diabetes, irrespective of whether they were treated with PIO or PLAC. Conclusions: 1) The protective effect of PIO on incidence of diabetes attenuates after discontinuation of therapy, 2) cumulative incidence of diabetes in individuals exposed to PIO remained significantly (56%) lower than PLAC and a greater number of PIO-treated individuals maintained NGT after median followup of 11.4 mo, and 3) low insulin secretion/insulin resistance index is a strong predictor of future diabetes following PIO discontinuation.",
author = "Devjit Tripathy and Schwenke, {Dawn C.} and Banerji, {Mary Ann} and Bray, {George A.} and Buchanan, {Thomas A.} and Clement, {Stephen C.} and Henry, {Robert R.} and Kitabchi, {Abbas E.} and Sunder Mudaliar and Ratner, {Robert E.} and Stentz, {Frankie B.} and Nicolas Musi and Reaven, {Peter D.} and DeFronzo, {Ralph A.}",
note = "Funding Information: This study was registered in ClinicalTrials.gov as trial number NCT00220961. This work was supported in part by GCRC Grant MO1-RR00221 at the University of Tennessee Health Science Center, Clinical and Translational Science Award Grant UL1TR000130 to the University of Southern California, and the South Texas Veterans Health Care System-Audie Murphy Division. The study was supported by an investigator-initiated and unrestricted research grant from Takeda Pharmaceuticals North America. Takeda Pharmaceuticals played no role in the study design, data collection/analysis, or manuscript preparation/review . The salaries of D.T. and R.A.D. are in part supported by the South Texas Veterans Health Care System. R.A.D. reports receiving grants from Amylin, Takeda, Bristol Myers Squibb, Astra Zeneca, and Janssen; serves on the advisory board for Amylin, Takeda, Bristol Myers Squibb, Novo Nordisk, Janssen, Astra Zeneca, Lexicon, and Boehringer Ingelheim; and is on the Speakers Bureau for Novo Nordisk, BMS, Janssen, and Astra Zeneca. R.A.D.'s salary is supported in part by the South Texas Veterans Health Care System-Audie L. Murphy Division. D.T. reports receiving consultant fees from HDL Diagnostics. D.C.S. reports receiving funding of the Phoenix Data Coordinating Center by a Takeda Grant. M.A.B. reports receiving consulting fees from Sanofi Aventis, Merck, Roche, and Boehringer Ingelheim; grants from Takeda and Merck; and fees for participation in review activities from Novartis and BMS. T.A.B. reports receiving grant support from Allergan and Takeda; advisory panel from Takeda; speakers bureau from Takeda; and stock options from Tethys Bioscience. S.C.C. reports that he is a full-time employee of Merck and Co. R.R.H. reports receiving grant support from AstraZeneca, BMS, Eli Lilly, Sanofi-Aventis, and Medtronics; is a consultant to Boehringer Ingelheim, Gilead, Intarcia, Isis, Eli Lilly, Novo Nordisk, Roche, and Medtronics; is on the advisory board to Amgen, AstraZeneca, BMS, Gilead, Intarcia, Johnson and Johnson/Janssen, Eli Lilly, Merck, Novo Nordisk, Roche, Sanofi-Aventis, Daiichi Sankyo, and Elcelyx. S.M. reports being a speaker to Takeda. R.E.R. reports receiving research support from Takeda. F.B.S. reports no conflict of interest. P.D.R. reports receiving research grants from BMS and Novo Nordisk, speaker support through Amylin, and is a consultant of BMS. G.A.B., A.E.K., and N.M. have nothing to disclose. Publisher Copyright: Copyright {\textcopyright} 2016 by the Endocrine Society.",
year = "2016",
month = may,
doi = "10.1210/jc.2015-4202",
language = "English (US)",
volume = "101",
pages = "2056--2062",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "5",
}