Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, placebo-controlled trial

Andrew J. Lewin, Mark S. Kipnes, Luigi F. Meneghini, Diane J. Plotkin, Inna T. Perevozskaya, Sukrut Shah, Darbie L. Maccubbin, Yale B. Mitchel, Jonathan A. Tobert

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background: Coronary heart disease is the major cause of mortality in individuals with diabetes mellitus (DM). Given the increasingly aggressive low-density lipoprotein cholesterol (LDL-C) goals for patients with DM set by the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association, many patients remain above target. Treatment with thiazolidinediones (TZDs) improves glycemic control but does not lower (and may raise) LDL-C concentrations. Objective: This study assessed the lipid-modifying efficacy and tolerability of adding the hydroxymethylglutaryl coenzyme A-reductase inhibitor simvastatin to existing TZD therapy in patients with type 2 DM. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Patients with type 2 DM who were taking a stable dose of pioglitazone or rosiglitazone and had a glycosylated hemoglobin (HbA1c) value ≤9.0% and an LDL-C concentration >100 mg/dL were randomized to receive simvastatin 40 mg (the recommended initial dose for patients with DM) or placebo for 24 weeks. The primary end point was the effect of treatment on LDL-C concentrations. Other lipid, lipoprotein, and safety measures were also assessed. Results: Two hundred fifty-three patients (127 [50.2%] men, 126 [49.8%] women; mean age, 56 years) were randomized to treatment (123 simvastatin, 130 placebo). At the end of the study, mean LDL-C concentrations were reduced 34.0% from baseline (from 134.3 to 89.5 mg/dL) in the simvastatin group and were unchanged in the placebo group (P < 0.001). Simvastatin produced significant reductions in concentrations of total cholesterol, triglycerides (TG), non-high-density lipoprotein cholesterol, and apolipoprotein (apo) B compared with placebo (all, P < 0.001) and significant increases in concentrations of high-density lipoprotein cholesterol (HDL-C) (P = 0.002) and apo A-I (P = 0.006). In patients who had not attained target concentrations of LDL-C (<100 mg/dL), TG (<150 mg/dL), or HDL-C (>45 mg/dL) at baseline, significantly more simvastatin recipients had achieved these goals at the end of the study compared with placebo recipients (LDL-C: 67.3% vs 5.2%, respectively, P < 0.001; HDL-C: 95.3% vs 83.6%, P < 0.05; TG: 40.8% vs 11.0%, P < 0.001). Simvastatin was well tolerated, and no clinically meaningful differences in the incidence of serious adverse events, treatment-related adverse events, or discontinuations due to adverse events were observed between groups. There were no significant between-group differences in glycemic control (HbA1c) or concentrations of fasting insulin, creatine phosphokinase, or hepatic transaminases. Conclusion: Simvastatin was an effective and generally well tolerated treatment for hyperlipidemia when used in combination with TZD therapy in this population of patients with type 2 DM.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalClinical Therapeutics
Volume26
Issue number3
DOIs
StatePublished - Mar 2004

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Simvastatin
LDL Cholesterol
Type 2 Diabetes Mellitus
Placebos
Lipids
Thiazolidinediones
Diabetes Mellitus
rosiglitazone
pioglitazone
Therapeutics
Hydroxymethylglutaryl-CoA Reductase Inhibitors
2,4-thiazolidinedione
Glycosylated Hemoglobin A
Creatine Kinase
Transaminases
Hyperlipidemias
Lipoproteins
Coronary Disease
Fasting
Oxidoreductases

Keywords

  • Goal attainment
  • Lipids
  • Simvastatin
  • Thiazolidinedione
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus : A multicenter, randomized, double-blind, placebo-controlled trial. / Lewin, Andrew J.; Kipnes, Mark S.; Meneghini, Luigi F.; Plotkin, Diane J.; Perevozskaya, Inna T.; Shah, Sukrut; Maccubbin, Darbie L.; Mitchel, Yale B.; Tobert, Jonathan A.

In: Clinical Therapeutics, Vol. 26, No. 3, 03.2004, p. 379-389.

Research output: Contribution to journalArticle

Lewin, Andrew J. ; Kipnes, Mark S. ; Meneghini, Luigi F. ; Plotkin, Diane J. ; Perevozskaya, Inna T. ; Shah, Sukrut ; Maccubbin, Darbie L. ; Mitchel, Yale B. ; Tobert, Jonathan A. / Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus : A multicenter, randomized, double-blind, placebo-controlled trial. In: Clinical Therapeutics. 2004 ; Vol. 26, No. 3. pp. 379-389.
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abstract = "Background: Coronary heart disease is the major cause of mortality in individuals with diabetes mellitus (DM). Given the increasingly aggressive low-density lipoprotein cholesterol (LDL-C) goals for patients with DM set by the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association, many patients remain above target. Treatment with thiazolidinediones (TZDs) improves glycemic control but does not lower (and may raise) LDL-C concentrations. Objective: This study assessed the lipid-modifying efficacy and tolerability of adding the hydroxymethylglutaryl coenzyme A-reductase inhibitor simvastatin to existing TZD therapy in patients with type 2 DM. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Patients with type 2 DM who were taking a stable dose of pioglitazone or rosiglitazone and had a glycosylated hemoglobin (HbA1c) value ≤9.0{\%} and an LDL-C concentration >100 mg/dL were randomized to receive simvastatin 40 mg (the recommended initial dose for patients with DM) or placebo for 24 weeks. The primary end point was the effect of treatment on LDL-C concentrations. Other lipid, lipoprotein, and safety measures were also assessed. Results: Two hundred fifty-three patients (127 [50.2{\%}] men, 126 [49.8{\%}] women; mean age, 56 years) were randomized to treatment (123 simvastatin, 130 placebo). At the end of the study, mean LDL-C concentrations were reduced 34.0{\%} from baseline (from 134.3 to 89.5 mg/dL) in the simvastatin group and were unchanged in the placebo group (P < 0.001). Simvastatin produced significant reductions in concentrations of total cholesterol, triglycerides (TG), non-high-density lipoprotein cholesterol, and apolipoprotein (apo) B compared with placebo (all, P < 0.001) and significant increases in concentrations of high-density lipoprotein cholesterol (HDL-C) (P = 0.002) and apo A-I (P = 0.006). In patients who had not attained target concentrations of LDL-C (<100 mg/dL), TG (<150 mg/dL), or HDL-C (>45 mg/dL) at baseline, significantly more simvastatin recipients had achieved these goals at the end of the study compared with placebo recipients (LDL-C: 67.3{\%} vs 5.2{\%}, respectively, P < 0.001; HDL-C: 95.3{\%} vs 83.6{\%}, P < 0.05; TG: 40.8{\%} vs 11.0{\%}, P < 0.001). Simvastatin was well tolerated, and no clinically meaningful differences in the incidence of serious adverse events, treatment-related adverse events, or discontinuations due to adverse events were observed between groups. There were no significant between-group differences in glycemic control (HbA1c) or concentrations of fasting insulin, creatine phosphokinase, or hepatic transaminases. Conclusion: Simvastatin was an effective and generally well tolerated treatment for hyperlipidemia when used in combination with TZD therapy in this population of patients with type 2 DM.",
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TY - JOUR

T1 - Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus

T2 - A multicenter, randomized, double-blind, placebo-controlled trial

AU - Lewin, Andrew J.

AU - Kipnes, Mark S.

AU - Meneghini, Luigi F.

AU - Plotkin, Diane J.

AU - Perevozskaya, Inna T.

AU - Shah, Sukrut

AU - Maccubbin, Darbie L.

AU - Mitchel, Yale B.

AU - Tobert, Jonathan A.

PY - 2004/3

Y1 - 2004/3

N2 - Background: Coronary heart disease is the major cause of mortality in individuals with diabetes mellitus (DM). Given the increasingly aggressive low-density lipoprotein cholesterol (LDL-C) goals for patients with DM set by the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association, many patients remain above target. Treatment with thiazolidinediones (TZDs) improves glycemic control but does not lower (and may raise) LDL-C concentrations. Objective: This study assessed the lipid-modifying efficacy and tolerability of adding the hydroxymethylglutaryl coenzyme A-reductase inhibitor simvastatin to existing TZD therapy in patients with type 2 DM. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Patients with type 2 DM who were taking a stable dose of pioglitazone or rosiglitazone and had a glycosylated hemoglobin (HbA1c) value ≤9.0% and an LDL-C concentration >100 mg/dL were randomized to receive simvastatin 40 mg (the recommended initial dose for patients with DM) or placebo for 24 weeks. The primary end point was the effect of treatment on LDL-C concentrations. Other lipid, lipoprotein, and safety measures were also assessed. Results: Two hundred fifty-three patients (127 [50.2%] men, 126 [49.8%] women; mean age, 56 years) were randomized to treatment (123 simvastatin, 130 placebo). At the end of the study, mean LDL-C concentrations were reduced 34.0% from baseline (from 134.3 to 89.5 mg/dL) in the simvastatin group and were unchanged in the placebo group (P < 0.001). Simvastatin produced significant reductions in concentrations of total cholesterol, triglycerides (TG), non-high-density lipoprotein cholesterol, and apolipoprotein (apo) B compared with placebo (all, P < 0.001) and significant increases in concentrations of high-density lipoprotein cholesterol (HDL-C) (P = 0.002) and apo A-I (P = 0.006). In patients who had not attained target concentrations of LDL-C (<100 mg/dL), TG (<150 mg/dL), or HDL-C (>45 mg/dL) at baseline, significantly more simvastatin recipients had achieved these goals at the end of the study compared with placebo recipients (LDL-C: 67.3% vs 5.2%, respectively, P < 0.001; HDL-C: 95.3% vs 83.6%, P < 0.05; TG: 40.8% vs 11.0%, P < 0.001). Simvastatin was well tolerated, and no clinically meaningful differences in the incidence of serious adverse events, treatment-related adverse events, or discontinuations due to adverse events were observed between groups. There were no significant between-group differences in glycemic control (HbA1c) or concentrations of fasting insulin, creatine phosphokinase, or hepatic transaminases. Conclusion: Simvastatin was an effective and generally well tolerated treatment for hyperlipidemia when used in combination with TZD therapy in this population of patients with type 2 DM.

AB - Background: Coronary heart disease is the major cause of mortality in individuals with diabetes mellitus (DM). Given the increasingly aggressive low-density lipoprotein cholesterol (LDL-C) goals for patients with DM set by the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association, many patients remain above target. Treatment with thiazolidinediones (TZDs) improves glycemic control but does not lower (and may raise) LDL-C concentrations. Objective: This study assessed the lipid-modifying efficacy and tolerability of adding the hydroxymethylglutaryl coenzyme A-reductase inhibitor simvastatin to existing TZD therapy in patients with type 2 DM. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Patients with type 2 DM who were taking a stable dose of pioglitazone or rosiglitazone and had a glycosylated hemoglobin (HbA1c) value ≤9.0% and an LDL-C concentration >100 mg/dL were randomized to receive simvastatin 40 mg (the recommended initial dose for patients with DM) or placebo for 24 weeks. The primary end point was the effect of treatment on LDL-C concentrations. Other lipid, lipoprotein, and safety measures were also assessed. Results: Two hundred fifty-three patients (127 [50.2%] men, 126 [49.8%] women; mean age, 56 years) were randomized to treatment (123 simvastatin, 130 placebo). At the end of the study, mean LDL-C concentrations were reduced 34.0% from baseline (from 134.3 to 89.5 mg/dL) in the simvastatin group and were unchanged in the placebo group (P < 0.001). Simvastatin produced significant reductions in concentrations of total cholesterol, triglycerides (TG), non-high-density lipoprotein cholesterol, and apolipoprotein (apo) B compared with placebo (all, P < 0.001) and significant increases in concentrations of high-density lipoprotein cholesterol (HDL-C) (P = 0.002) and apo A-I (P = 0.006). In patients who had not attained target concentrations of LDL-C (<100 mg/dL), TG (<150 mg/dL), or HDL-C (>45 mg/dL) at baseline, significantly more simvastatin recipients had achieved these goals at the end of the study compared with placebo recipients (LDL-C: 67.3% vs 5.2%, respectively, P < 0.001; HDL-C: 95.3% vs 83.6%, P < 0.05; TG: 40.8% vs 11.0%, P < 0.001). Simvastatin was well tolerated, and no clinically meaningful differences in the incidence of serious adverse events, treatment-related adverse events, or discontinuations due to adverse events were observed between groups. There were no significant between-group differences in glycemic control (HbA1c) or concentrations of fasting insulin, creatine phosphokinase, or hepatic transaminases. Conclusion: Simvastatin was an effective and generally well tolerated treatment for hyperlipidemia when used in combination with TZD therapy in this population of patients with type 2 DM.

KW - Goal attainment

KW - Lipids

KW - Simvastatin

KW - Thiazolidinedione

KW - Type 2 diabetes mellitus

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