Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

OBJECTIVE The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke andmyocardial infarction in patientswith insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on themetabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention. RESEARCH DESIGN AND METHODS A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG) <126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score >3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing. RESULTS At baseline, the mean FPG, HbA 1c , insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8% (40 mmol/mol), 22.4 mIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P < 0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8%) participants assigned to pioglitazone compared with 149 (7.7%) assigned to placebo (hazard ratio [HR] 0.48 [95% CI 0.33-0.69]; P < 0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG >100 mg/dL [5.6 mmol/L]; HR 0.41 [95% CI 0.30-0.57]) or elevated HbA 1c (>5.7% [39 mmol/mol]; HR 0.46 [0.34-0.62]). CONCLUSIONS Among patientswith insulin resistance butwithout diabeteswho had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial.

Original languageEnglish (US)
Pages (from-to)1684-1692
Number of pages9
JournalDiabetes care
Volume39
Issue number10
DOIs
StatePublished - Oct 1 2016

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pioglitazone
Cerebrovascular Disorders
Insulin Resistance
Stroke
Fasting
Transient Ischemic Attack
Glucose
Placebos
Infarction
Research Design
Interviews
Insulin

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Inzucchi, S. E., Viscoli, C. M., Young, L. H., Furie, K. L., Gorman, M., Lovejoy, A. M., ... Kernan, W. N. (2016). Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes care, 39(10), 1684-1692. https://doi.org/10.2337/dc16-0798

Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. / Inzucchi, Silvio E.; Viscoli, Catherine M.; Young, Lawrence H.; Furie, Karen L.; Gorman, Mark; Lovejoy, Anne M.; Dagogo-Jack, Samuel; Ismail-Beigi, Faramarz; Korytkowski, Mary T.; Pratley, Richard E.; Schwartz, Gregory G.; Kernan, Walter N.

In: Diabetes care, Vol. 39, No. 10, 01.10.2016, p. 1684-1692.

Research output: Contribution to journalArticle

Inzucchi, SE, Viscoli, CM, Young, LH, Furie, KL, Gorman, M, Lovejoy, AM, Dagogo-Jack, S, Ismail-Beigi, F, Korytkowski, MT, Pratley, RE, Schwartz, GG & Kernan, WN 2016, 'Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease', Diabetes care, vol. 39, no. 10, pp. 1684-1692. https://doi.org/10.2337/dc16-0798
Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes care. 2016 Oct 1;39(10):1684-1692. https://doi.org/10.2337/dc16-0798
Inzucchi, Silvio E. ; Viscoli, Catherine M. ; Young, Lawrence H. ; Furie, Karen L. ; Gorman, Mark ; Lovejoy, Anne M. ; Dagogo-Jack, Samuel ; Ismail-Beigi, Faramarz ; Korytkowski, Mary T. ; Pratley, Richard E. ; Schwartz, Gregory G. ; Kernan, Walter N. / Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. In: Diabetes care. 2016 ; Vol. 39, No. 10. pp. 1684-1692.
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abstract = "OBJECTIVE The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke andmyocardial infarction in patientswith insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on themetabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention. RESEARCH DESIGN AND METHODS A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG) <126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score >3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing. RESULTS At baseline, the mean FPG, HbA 1c , insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8{\%} (40 mmol/mol), 22.4 mIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P < 0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8{\%}) participants assigned to pioglitazone compared with 149 (7.7{\%}) assigned to placebo (hazard ratio [HR] 0.48 [95{\%} CI 0.33-0.69]; P < 0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG >100 mg/dL [5.6 mmol/L]; HR 0.41 [95{\%} CI 0.30-0.57]) or elevated HbA 1c (>5.7{\%} [39 mmol/mol]; HR 0.46 [0.34-0.62]). CONCLUSIONS Among patientswith insulin resistance butwithout diabeteswho had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial.",
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AU - Inzucchi, Silvio E.

AU - Viscoli, Catherine M.

AU - Young, Lawrence H.

AU - Furie, Karen L.

AU - Gorman, Mark

AU - Lovejoy, Anne M.

AU - Dagogo-Jack, Samuel

AU - Ismail-Beigi, Faramarz

AU - Korytkowski, Mary T.

AU - Pratley, Richard E.

AU - Schwartz, Gregory G.

AU - Kernan, Walter N.

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N2 - OBJECTIVE The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke andmyocardial infarction in patientswith insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on themetabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention. RESEARCH DESIGN AND METHODS A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG) <126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score >3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing. RESULTS At baseline, the mean FPG, HbA 1c , insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8% (40 mmol/mol), 22.4 mIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P < 0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8%) participants assigned to pioglitazone compared with 149 (7.7%) assigned to placebo (hazard ratio [HR] 0.48 [95% CI 0.33-0.69]; P < 0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG >100 mg/dL [5.6 mmol/L]; HR 0.41 [95% CI 0.30-0.57]) or elevated HbA 1c (>5.7% [39 mmol/mol]; HR 0.46 [0.34-0.62]). CONCLUSIONS Among patientswith insulin resistance butwithout diabeteswho had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial.

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