The Glucose and Lipid Assessment in Diabetes (GLAD) trial

Results from phase II study of tesaglitazar for patients with type 2 diabetes suggest the drug can significantly improve blood levels of triglycerides and high-density lipoprotein cholesterol in addition to improving blood glucose control, according to a Late Breaking Clinical Trial presentation at the annual meeting of the American Diabetes Association.

The GLAD study was a 12-week, randomized, double-blind, placebo-controlled, dose-ranging study in 500 patients. The primary study objective was to observe drug effects on fasting plasma glucose. Secondary endpoints included lipid variables and fasting plasma insulin. Based on the study’s results, the 0.5 mg and 1.0 mg doses will proceed to phase III development.

Specifically, researchers found a dose-dependent reduction in fasting glucose of up to 61 mg/dL. Patients receiving 1.0 mg had reductions of up to 41 mg/dL.
Improvements in lipid profiles were also significant. There was a dose-dependent reduction in fasting triglyceride level of up to 41 percent, with a 33 percent reduction at 1.0 mg dose. The dose-dependent increase in high-density lipoprotein cholesterol level was maximal (15 percent) with a 1.0 mg dose. Dose-dependent reduction in low-density lipoprotein cholesterol was significant for the highest doses tested, but nonsignificant (at 6 percent) for 1.0 mg dose.

No new cases of congestive heart failure were reported during the study duration. Tesaglitazar produced weight gains of approximately 1 kg at the 0.5-mg and 1.0-mg dose.

"The past focus in type 2 diabetes management has been glucose; however, there is an increasing need for a single agent that can target both glucose and dyslipidemia associated with type 2 diabetes," said lead investigator Barry J. Goldstein, MD, PhD, Director of the Division of Endocrinology, Diabetes and Metabolic Diseases at Jefferson Medical College, Philadelphia, PA. "The GLAD study provides new insights on treating both glucose and lipid abnormalities in type 2 diabetes, and potentially, its underlying metabolic defects."

GALIDA(TM) (tesaglitazar) is an investigational oral drug being evaluated as a once-daily treatment for patients with type 2 diabetes. It is among the first of a new class of compounds [peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonists] proposed to act upon both PPAR alpha and gamma receptors to modify both lipids and insulin resistance in patients with type 2 diabetes.