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Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes.
Clin Ther. 2005 Aug; 27(8):1181-95.CT

Abstract

BACKGROUND

Peroxisome proliferator-activated receptors (PPARs) present a therapeutic target, and simultaneous activation of PPAR-alpha and PPAR-gamma may provide improvements in glycemic control and dyslipidemia in patients with type 2 diabetes.

OBJECTIVE

The goal of this study was to evaluate the efficacy and safety of muraglitazar, a dual (alpha/gamma) PPAR activator, in adult patients with type 2 diabetes whose disease was inadequately controlled by diet and exercise.

METHODS

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 24-week monotherapy study in drug-naive, type 2 diabetes patients with inadequate glycemic control. Men and women aged 18 to 70 years with a body mass index < or =41 kg/m(2) and serum triglyceride levels < or =600 mg/dL were eligible for study participation. The study included double-blind and open-label treatment phases. Patients with glycosylated hemoglobin (HbA(1c)) levels > or =7.0% and < or =10.0% at screening were enrolled in the double-blind treatment phase. These patients received treatment with muraglitazar 2.5 mg, muraglitazar 5 mg, or placebo. Patients with HbA(1c) levels >10.0% and < or =12.0% who met all other study criteria were eligible for enrollment in a 24-week, open-label evaluation of muraglitazar 5 mg. The primary end point was the mean change from baseline in HbA(1c) levels after 24 weeks of treatment.

RESULTS

A total of 340 patients (179 men, 161 women) participated in the double-blind treatment phase of the study. Patients had mean baseline HbA(1c) levels of 7.9% to 8.0%. Monotherapy with muraglitazar 2.5 and 5 mg significantly reduced HbA(1c) levels (-1.05% and -1.23%, respectively) compared with placebo (-0.32%; P < 0.001). At week 24, 58%, 72%, and 30% of the patients receiving muraglitazar 2.5 mg, muraglitazar 5 mg, and placebo, respectively, achieved the American Diabetes Association-recommended HbA(1c) goal of <7.0%. Fasting plasma glucose, free fatty acids, and fasting plasma insulin levels significantly decreased during muraglitazar treatment (P < 0.001), suggesting an increase in insulin sensitivity. Muraglitazar 2.5 and 5 mg provided improvements from baseline in triglyceride (-18% and -27%), high-density lipoprotein (HDL) cholesterol (10% and 16%), apolipoprotein B (-7% and -12%), and non-HDL cholesterol levels (-3% and -5%) (P < 0.05 vs placebo for each). In a parallel, open-label cohort of 109 drug-naive patients (56 men, 53 women; mean baseline HbA(1c) level, 10.6%), muraglitazar 5 mg decreased the overall mean HbA(1c) level from baseline by 2.62% (last observation carried forward) and by 3.49% in the 62 patients completing 24 weeks of study. Changes in lipid parameters during open-label treatment were similar to those observed during double-blind treatment. Muraglitazar was generally well tolerated. Edema-related adverse events of mild to moderate severity occurred in 8% to 11% of patients in all groups. Mean changes from baseline weight in the double-blind treatment groups were 1.1 kg for muraglitazar 2.5 mg, 2.1 kg for muraglitazar 5 mg, and -0.8 kg for placebo (P < 0.001); there was a mean 2.9-kg increase in the open-label muraglitazar 5-mg group.

CONCLUSION

In this study, 24 weeks of treatment with muraglitazar 2.5 or 5 mg was an effective treatment option for these patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise.

Authors+Show Affiliations

University of North Carolina School of Medicine, Chapel Hill, 27599, USA. jbuse@med.unc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16199244

Citation

Buse, John B., et al. "Muraglitazar, a Dual (alpha/gamma) PPAR Activator: a Randomized, Double-blind, Placebo-controlled, 24-week Monotherapy Trial in Adult Patients With Type 2 Diabetes." Clinical Therapeutics, vol. 27, no. 8, 2005, pp. 1181-95.
Buse JB, Rubin CJ, Frederich R, et al. Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. Clin Ther. 2005;27(8):1181-95.
Buse, J. B., Rubin, C. J., Frederich, R., Viraswami-Appanna, K., Lin, K. C., Montoro, R., Shockey, G., & Davidson, J. A. (2005). Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. Clinical Therapeutics, 27(8), 1181-95.
Buse JB, et al. Muraglitazar, a Dual (alpha/gamma) PPAR Activator: a Randomized, Double-blind, Placebo-controlled, 24-week Monotherapy Trial in Adult Patients With Type 2 Diabetes. Clin Ther. 2005;27(8):1181-95. PubMed PMID: 16199244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. AU - Buse,John B, AU - Rubin,Cindy J, AU - Frederich,Robert, AU - Viraswami-Appanna,Kalyanee, AU - Lin,Kwo-Chuan, AU - Montoro,Rafael, AU - Shockey,Gerald, AU - Davidson,Jaime A, PY - 2005/06/15/accepted PY - 2005/10/4/pubmed PY - 2006/7/22/medline PY - 2005/10/4/entrez SP - 1181 EP - 95 JF - Clinical therapeutics JO - Clin Ther VL - 27 IS - 8 N2 - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) present a therapeutic target, and simultaneous activation of PPAR-alpha and PPAR-gamma may provide improvements in glycemic control and dyslipidemia in patients with type 2 diabetes. OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of muraglitazar, a dual (alpha/gamma) PPAR activator, in adult patients with type 2 diabetes whose disease was inadequately controlled by diet and exercise. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 24-week monotherapy study in drug-naive, type 2 diabetes patients with inadequate glycemic control. Men and women aged 18 to 70 years with a body mass index < or =41 kg/m(2) and serum triglyceride levels < or =600 mg/dL were eligible for study participation. The study included double-blind and open-label treatment phases. Patients with glycosylated hemoglobin (HbA(1c)) levels > or =7.0% and < or =10.0% at screening were enrolled in the double-blind treatment phase. These patients received treatment with muraglitazar 2.5 mg, muraglitazar 5 mg, or placebo. Patients with HbA(1c) levels >10.0% and < or =12.0% who met all other study criteria were eligible for enrollment in a 24-week, open-label evaluation of muraglitazar 5 mg. The primary end point was the mean change from baseline in HbA(1c) levels after 24 weeks of treatment. RESULTS: A total of 340 patients (179 men, 161 women) participated in the double-blind treatment phase of the study. Patients had mean baseline HbA(1c) levels of 7.9% to 8.0%. Monotherapy with muraglitazar 2.5 and 5 mg significantly reduced HbA(1c) levels (-1.05% and -1.23%, respectively) compared with placebo (-0.32%; P < 0.001). At week 24, 58%, 72%, and 30% of the patients receiving muraglitazar 2.5 mg, muraglitazar 5 mg, and placebo, respectively, achieved the American Diabetes Association-recommended HbA(1c) goal of <7.0%. Fasting plasma glucose, free fatty acids, and fasting plasma insulin levels significantly decreased during muraglitazar treatment (P < 0.001), suggesting an increase in insulin sensitivity. Muraglitazar 2.5 and 5 mg provided improvements from baseline in triglyceride (-18% and -27%), high-density lipoprotein (HDL) cholesterol (10% and 16%), apolipoprotein B (-7% and -12%), and non-HDL cholesterol levels (-3% and -5%) (P < 0.05 vs placebo for each). In a parallel, open-label cohort of 109 drug-naive patients (56 men, 53 women; mean baseline HbA(1c) level, 10.6%), muraglitazar 5 mg decreased the overall mean HbA(1c) level from baseline by 2.62% (last observation carried forward) and by 3.49% in the 62 patients completing 24 weeks of study. Changes in lipid parameters during open-label treatment were similar to those observed during double-blind treatment. Muraglitazar was generally well tolerated. Edema-related adverse events of mild to moderate severity occurred in 8% to 11% of patients in all groups. Mean changes from baseline weight in the double-blind treatment groups were 1.1 kg for muraglitazar 2.5 mg, 2.1 kg for muraglitazar 5 mg, and -0.8 kg for placebo (P < 0.001); there was a mean 2.9-kg increase in the open-label muraglitazar 5-mg group. CONCLUSION: In this study, 24 weeks of treatment with muraglitazar 2.5 or 5 mg was an effective treatment option for these patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/16199244/Muraglitazar_a_dual__alpha/gamma__PPAR_activator:_a_randomized_double_blind_placebo_controlled_24_week_monotherapy_trial_in_adult_patients_with_type_2_diabetes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(05)00153-0 DB - PRIME DP - Unbound Medicine ER -