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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2056-2062
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number5
DOIs
StatePublished - May 1 2016

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pioglitazone
Medical problems
Glucose
Incidence
Placebos
Insulin
Glucose Intolerance
Therapeutics
Insulin Resistance
Thiazolidinediones

ASJC Scopus subject areas

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

Cite this

Diabetes incidence and glucose tolerance after termination of pioglitazone therapy : Results from ACT NOW. / Tripathy, Devjit; Schwenke, Dawn C.; Banerji, Mary Ann; Bray, George A.; Buchanan, Thomas A.; Clement, Stephen C.; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Musi, Nicolas; Reaven, Peter D.; Defronzo, Ralph A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 5, 01.05.2016, p. 2056-2062.

Research output: Contribution to journalArticle

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
Tripathy, Devjit ; Schwenke, Dawn C. ; Banerji, Mary Ann ; Bray, George A. ; Buchanan, Thomas A. ; Clement, Stephen C. ; Henry, Robert R. ; Kitabchi, Abbas E. ; Mudaliar, Sunder ; Ratner, Robert E. ; Stentz, Frankie B. ; Musi, Nicolas ; Reaven, Peter D. ; Defronzo, Ralph A. / Diabetes incidence and glucose tolerance after termination of pioglitazone therapy : Results from ACT NOW. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 5. pp. 2056-2062.
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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.",
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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

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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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