The effects of tesaglitazar as add-on treatment to metformin in patients with poorly controlled type 2 diabetes.
This study assessed the effects of tesaglitazar (0.5 or 1 mg/day), a dual peroxisome proliferator-activated receptor alpha/gamma agonist, when added to maximally tolerated metformin (2-2.5 g/day) in patients with poorly controlled type 2 diabetes. The primary end point of this 24-week, randomised, placebo-controlled study was the absolute change from baseline in glycosylated haemoglobin (HbA1C). Tesaglitazar significantly reduced HbA1C, fasting plasma glucose and insulin levels compared with placebo (p<0.0001 for all) when added to metformin. Triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C levels also improved with tesaglitazar treatment (p<0.0001 for all). Adverse events were generally similar across treatments, except for higher frequencies of peripheral oedema and weight gain in the tesaglitazar 1 mg group. Although reversibility was not fully evaluated, dose-dependent changes in mean serum creatinine levels and haematology measures tended to return towards baseline at follow-up. Despite the clinical discontinuation of tesaglitazar, this study has demonstrated the potential benefits of dual PPAR agonism as add-on therapy to metformin, in patients with poorly controlled type 2 diabetes.
Göke
Burkhard
B
Department of Internal Medicine II, University of Munich-Grosshadern, Marchinioninstr. 15, 81377 Munich, Germany. Burkhard.Goeke@med.uni-muenchen.de
Gause-Nilsson
Ingrid
I
Persson
Anders
A
D000328:Adult; D000368:Aged; D000476:Alkanesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003404:Creatinine / 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 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D000476:Alkanesulfonates; D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; C501413:tesaglitazar