By Louise Gagnon
TORONTO, CANADA -- June 4, 2007 -- An experimental compound has demonstrated effective glycemic control and improvement in dyslipidemia in type 2 diabetics, according to research presented at a poster session here at the 89th annual meeting of the Endocrine Society (ENDO).
Dubbed DIO-902, an enantiomer of ketoconazole, the compound was administered in type 2 diabetes patients who were drug naïve - they had been treated with diet and exercise alone or were on stable metformin.
"This was a dose-finding study," said Bernice Welles, MD, one of the study's investigators and vice-president of development, DiObex Inc., San Francisco, California, United States. "The therapy improves glycemic control and as well positively affects lipid levels. The effect on lipids is important because type 2 diabetic patients are at increased risk for cardiovascular illness."
Dr. Welles noted that ketoconazole, a racemic combination of two enantiomers, has been used to treat cortisol excess in patients with Cushing's syndrome, the results of which have led to improved insulin resistance, glycemic control, lipid measures, and blood pressure. Pre-clinical data has suggested that the novel compound may offer greater efficacy and safety than ketoconazole as a therapy, said Dr. Welles.
The researchers recruited 37 patients, aged 18 to 70, who had type 2 diabetes for at least six months. Their HbA1c level ranged from 6.5% to 10.9% and their body mass index measured 26 to 40. Patients were randomised to one of five arms including placebo (six patients), 400 mg of ketoconazole (eight patients), 200 mg of DIO-902 (10 patients), 400 mg of DIO-902 (six patients), and 600 mg of DIO-902 (three patients).
Dr. Welles noted subjects underwent a 3-week washout period to eliminate any effect of existing lipid-lowering therapies. They were on their therapy for two weeks and then followed for two weeks after treatment.
When looking at glycemic measures, fructosamine levels decreased by 2.3 umol/l in the placebo and ketoconazole arms of the study. The levels were reduced by 12.2, 8.3, and 29.3 umol/l in the 200 mg, 400 mg, and 600 mg arms, respectively.
Moreover, C-reactive protein, which Dr. Welles stressed was a marker of inflammation, was elevated in the placebo and ketoconazole arms, but fell in a dose-dependent fashion in the three study groups where DIO-902 was administered. The reductions ranged from 28% to 48% (J-T trend test, P =.27).
Similarly, a dose-dependent decrease (J-T trend test, P <.001) was seen in all DIO-902 treated patients, with total cholesterol reductions ranging from 12% to 33% and LDL-cholesterol reductions ranging from 12% to 44%.
Dr. Welles noted patients experienced adverse events of a gastrointestinal nature such as bloating and nausea, but that no patients withdrew from the study because of adverse events. Patients had a normal cortisol response to ACTH stimulation testing when it was performed within 24 hours after the last dose of study drug.
Future research will look at the effect of administering another set of doses of DIO-902 in several hundred patients, said Dr. Welles.
The study was funded by DiObex Inc., the manufacturer of DIO-902.
[Presentation title: Effects of 14-Day Treatment with DIO-902 on Lipids and Glycemic Control: Results of a Randomized Placebo-Controlled Trial in Patients with Type 2 Diabetes. Abstract P2-243]
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