Efficacy, safety and tolerability of tesaglitazar when added to the therapeutic regimen of poorly controlled insulin-treated patients with type 2 diabetes.
This randomised, double-blind, parallel-group study assessed the effects of addition of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, tesaglitazar, for 24 weeks to the therapeutic regimen of 392 poorly controlled (glycosylated haemoglobin [HbA1C] 7.5-10%) insulin-treated, type 2 diabetes patients. At 24 weeks, tesaglitazar 0.5 mg resulted in a 0.66% (95% confidence intervals: -0.85, -0.47; p<0.0001) reduction from baseline in HbA1C, and reduced fasting plasma glucose (p<0.0001) and daily insulin dose (p=0.014) versus placebo. After 24 weeks, tesaglitazar caused greater improvements from baseline in triglycerides (p<0.0001), high-density lipoprotein cholesterol (HDL-C) (p<0.001), non-HDL-C (p<0.05), apolipoprotein (apo)A-I (p<0.05) and apoB levels (p<0.01) than placebo. Tesaglitazar was generally well tolerated but was associated with a greater increase in serum creatinine level than placebo. The clinical development of tesaglitazar is no longer continuing; its effects on the glucose and lipid abnormalities of type 2 diabetes suggest that the concept of dual PPARalpha/gamma agonism is worthy of further investigation.
Ratner
Robert E
RE
MedStar Research Institute, Hyattsville, MD 20783, USA. Robert.Ratner@MedStar.net
Parikh
Shamik
S
Tou
Conrad
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000476:Alkanesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000476:Alkanesulfonates; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; D014280:Triglycerides; C501413:tesaglitazar