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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.

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 < or =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.)% 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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  • Authors+Show Affiliations

    ,

    National Research Institute, Los Angeles, California 90057, USA. docl@sbcglobal.net

    , , , , , , , ,

    Source

    Clinical therapeutics 26:3 2004 Mar pg 379-89

    MeSH

    Adult
    Aged
    Cholesterol, LDL
    Diabetes Mellitus, Type 2
    Double-Blind Method
    Drug Therapy, Combination
    Female
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Hyperlipoproteinemias
    Male
    Middle Aged
    Pioglitazone
    Rosiglitazone
    Simvastatin
    Thiazolidinediones

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    15110130

    Citation

    Lewin, Andrew J., et al. "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." Clinical Therapeutics, vol. 26, no. 3, 2004, pp. 379-89.
    Lewin AJ, Kipnes MS, Meneghini LF, et al. 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. Clin Ther. 2004;26(3):379-89.
    Lewin, A. J., Kipnes, M. S., Meneghini, L. F., Plotkin, D. J., Perevozskaya, I. T., Shah, S., ... Tobert, J. A. (2004). 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. Clinical Therapeutics, 26(3), pp. 379-89.
    Lewin AJ, et al. 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. Clin Ther. 2004;26(3):379-89. PubMed PMID: 15110130.
    * Article titles in AMA citation format should be in sentence-case
    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: 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, AU - ,, PY - 2004/01/21/accepted PY - 2004/4/28/pubmed PY - 2004/8/17/medline PY - 2004/4/28/entrez SP - 379 EP - 89 JF - Clinical therapeutics JO - Clin Ther VL - 26 IS - 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 < or =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.)% 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. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/15110130/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149291804900331 DB - PRIME DP - Unbound Medicine ER -