Coadministration of muraglitazar plus glyburide: improvement of glycaemic and lipid profiles in patients with type 2 diabetes.
In this trial we evaluated the efficacy and safety of muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, plus glyburide in patients with type 2 diabetes not controlled with sulphonylurea monotherapy. After 2 weeks of open-label glyburide (15 mg/day), 583 patients were randomised to additionally receive muraglitazar 2.5 mg, 5 mg, or placebo. End points included changes in HbA(1C) and fasting plasma glucose (FPG) at weeks 24 and 102, and changes in lipid parameters at weeks 11/12 and 102.At week 24, mean changes from baseline in HbA(1C) and FPG were significantly greater with glyburide plus muraglitazar 2.5 mg or 5 mg than with glyburide plus placebo (p<0.0001). At week 11/12, triglyceride levels were significantly reduced with muraglitazar (p<0.0001). During the extension phase, muraglitazar demonstrated long-term glycaemic and lipid effects through week 102. Although generally well tolerated, muraglitazar was associated with higher rates of congestive heart failure, cardiovascular events, weight gain and oedema.
Rubin
Cindy J
CJ
Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA. cindy.rubin@bms.com
De Pril
Veerle
V
Fiedorek
Fred T
FT
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D005905:Glyburide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism*; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D005998:Glycine; D007004:Hypoglycemic Agents; D008055:Lipids; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; C517652:hemoglobin A1c protein, human; C500085:muraglitazar