Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW

Devjit Tripathy; Dawn C. Schwenke; Mary Ann Banerji; George A. Bray; Thomas A. Buchanan; Stephen C. Clement; Robert R. Henry; Abbas E. Kitabchi; Sunder Mudaliar; Robert E. Ratner; Frankie B. Stentz; Nicolas Musi; Peter D. Reaven; Ralph A. DeFronzo

doi:10.1210/jc.2015-4202

Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW

Devjit Tripathy, Dawn C. Schwenke, Mary Ann Banerji, George A. Bray, Thomas A. Buchanan, Stephen C. Clement, Robert R. Henry, Abbas E. Kitabchi, Sunder Mudaliar, Robert E. Ratner, Frankie B. Stentz, Nicolas Musi, Peter D. Reaven, Ralph A. DeFronzo

Department of Medicine

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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 (I_0-120 /G_0-120 × 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.

Original language	English (US)
Pages (from-to)	2056-2062
Number of pages	7
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	101
Issue number	5
DOIs	https://doi.org/10.1210/jc.2015-4202
State	Published - May 2016

ASJC Scopus subject areas

Biochemistry, medical
Endocrinology
Biochemistry
Clinical Biochemistry
Endocrinology, Diabetes and Metabolism

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10.1210/jc.2015-4202

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Tripathy, D., Schwenke, D. C., Banerji, M. A., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Kitabchi, A. E., Mudaliar, S., Ratner, R. E., Stentz, F. B., Musi, N., Reaven, P. D., & DeFronzo, R. A. (2016). Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW. Journal of Clinical Endocrinology and Metabolism, 101(5), 2056-2062. https://doi.org/10.1210/jc.2015-4202

Tripathy, D, Schwenke, DC, Banerji, MA, Bray, GA, Buchanan, TA, Clement, SC, Henry, RR, Kitabchi, AE, Mudaliar, S, Ratner, RE, Stentz, FB, Musi, N, Reaven, PD & DeFronzo, RA 2016, 'Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 5, pp. 2056-2062. https://doi.org/10.1210/jc.2015-4202

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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 = "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",

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T1 - Diabetes incidence and glucose tolerance after termination of pioglitazone therapy

T2 - Results from ACT NOW

AU - Tripathy, Devjit

AU - Schwenke, Dawn C.

AU - Banerji, Mary Ann

AU - Bray, George A.

AU - Buchanan, Thomas A.

AU - Clement, Stephen C.

AU - Henry, Robert R.

AU - Kitabchi, Abbas E.

AU - Mudaliar, Sunder

AU - Ratner, Robert E.

AU - Stentz, Frankie B.

AU - Musi, Nicolas

AU - Reaven, Peter D.

AU - DeFronzo, Ralph A.

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

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Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: Results from ACT NOW

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