Devjit Tripathy1, Dawn C Schwenke1, MaryAnn Banerji1, George A Bray1, Thomas A Buchanan1, Stephen C Clement1, Robert R Henry1, Abbas E Kitabchi1, Sunder Mudaliar1, Robert E Ratner1, Frankie B Stentz1, Nicolas Musi1, Peter D Reaven1, Ralph A DeFronzo1. 1. Texas Diabetes Institute and University of Texas Health Science Center (D.T., N.M., R.A.D.), South Texas Veterans Health Care System, San Antonio, Texas 78229; Phoenix VA Health Care System (D.C.S., P.D.R.), Phoenix, Arizona 85012; College of Nursing & Health Innovation (D.C.S.), Arizona State University, Phoenix, Arizona 85281; SUNY Health Science Center at Brooklyn (M.A.B.), Brooklyn, New York 11203; Pennington Biomedical Research Center (G.A.B.), Louisiana State University, Baton Rouge, Louisiana 70803; University of Southern California Keck School of Medicine (T.A.B.), Los Angeles, California; Inova Fairfax Hospital (S.C.C.), Falls Church, Virginia 22042; VA San Diego Healthcare System and University of California, San Diego (R.R.H., S.M.), San Diego, California 92093; Division of Endocrinology, Diabetes and Metabolism (A.E.K., F.B.S.), University of Tennessee-Memphis, Memphis, Tennessee; and Medstar Research Institute (R.E.R.), Hyattsville, Maryland 20782.
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.
RCT Entities:
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.
Authors: Ralph A DeFronzo; Devjit Tripathy; Dawn C Schwenke; MaryAnn Banerji; George A Bray; Thomas A Buchanan; Stephen C Clement; Robert R Henry; Howard N Hodis; Abbas E Kitabchi; Wendy J Mack; Sunder Mudaliar; Robert E Ratner; Ken Williams; Frankie B Stentz; Nicolas Musi; Peter D Reaven Journal: N Engl J Med Date: 2011-03-24 Impact factor: 91.245
Authors: D J Magliano; J E Shaw; S M Shortreed; W J Nusselder; D Liew; E L M Barr; P Z Zimmet; A Peeters Journal: Diabetologia Date: 2008-09-23 Impact factor: 10.122
Authors: Ralph A Defronzo; Devjit Tripathy; Dawn C Schwenke; Maryann Banerji; George A Bray; Thomas A Buchanan; Stephen C Clement; Amalia Gastaldelli; Robert R Henry; Abbas E Kitabchi; Sunder Mudaliar; Robert E Ratner; Frankie B Stentz; Nicolas Musi; Peter D Reaven Journal: Diabetes Date: 2013-07-17 Impact factor: 9.461
Authors: Silvio E Inzucchi; Catherine M Viscoli; Lawrence H Young; Karen L Furie; Mark Gorman; Anne M Lovejoy; Samuel Dagogo-Jack; Faramarz Ismail-Beigi; Mary T Korytkowski; Richard E Pratley; Gregory G Schwartz; Walter N Kernan Journal: Diabetes Care Date: 2016-07-27 Impact factor: 19.112