Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes

The ACCORD lipid trial

Peter E. Linz, Laura C. Lovato, Robert P. Byington, Patrick J. O'Connor, Lawrence A. Leiter, Daniel Weiss, Rex W. Force, John R. Crouse, Faramarz Ismail-Beigi, Debra L. Simmons, Vasilios Papademetriou, Henry N. Ginsberg, Marshall Elam

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

OBJECTIVE To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization). CONCLUSIONS Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.

Original languageEnglish (US)
Pages (from-to)686-693
Number of pages8
JournalDiabetes care
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2014

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Fenofibrate
Type 2 Diabetes Mellitus
HDL Cholesterol
Lipids
Placebos
Therapeutics
Simvastatin
Canada
2,4-thiazolidinedione
Research Design
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

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

Cite this

Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes : The ACCORD lipid trial. / Linz, Peter E.; Lovato, Laura C.; Byington, Robert P.; O'Connor, Patrick J.; Leiter, Lawrence A.; Weiss, Daniel; Force, Rex W.; Crouse, John R.; Ismail-Beigi, Faramarz; Simmons, Debra L.; Papademetriou, Vasilios; Ginsberg, Henry N.; Elam, Marshall.

In: Diabetes care, Vol. 37, No. 3, 01.03.2014, p. 686-693.

Research output: Contribution to journalArticle

Linz, PE, Lovato, LC, Byington, RP, O'Connor, PJ, Leiter, LA, Weiss, D, Force, RW, Crouse, JR, Ismail-Beigi, F, Simmons, DL, Papademetriou, V, Ginsberg, HN & Elam, M 2014, 'Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: The ACCORD lipid trial', Diabetes care, vol. 37, no. 3, pp. 686-693. https://doi.org/10.2337/dc13-0790
Linz, Peter E. ; Lovato, Laura C. ; Byington, Robert P. ; O'Connor, Patrick J. ; Leiter, Lawrence A. ; Weiss, Daniel ; Force, Rex W. ; Crouse, John R. ; Ismail-Beigi, Faramarz ; Simmons, Debra L. ; Papademetriou, Vasilios ; Ginsberg, Henry N. ; Elam, Marshall. / Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes : The ACCORD lipid trial. In: Diabetes care. 2014 ; Vol. 37, No. 3. pp. 686-693.
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title = "Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: The ACCORD lipid trial",
abstract = "OBJECTIVE To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106{\%} higher among those randomized to fenofibrate (10.1{\%} fenofibrate vs. 4.9{\%} placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0{\%} for both vs. 2.2{\%} for neither at 48 months postrandomization). CONCLUSIONS Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.",
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AU - Linz, Peter E.

AU - Lovato, Laura C.

AU - Byington, Robert P.

AU - O'Connor, Patrick J.

AU - Leiter, Lawrence A.

AU - Weiss, Daniel

AU - Force, Rex W.

AU - Crouse, John R.

AU - Ismail-Beigi, Faramarz

AU - Simmons, Debra L.

AU - Papademetriou, Vasilios

AU - Ginsberg, Henry N.

AU - Elam, Marshall

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N2 - OBJECTIVE To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization). CONCLUSIONS Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.

AB - OBJECTIVE To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization). CONCLUSIONS Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.

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