The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied during six successive 2-wk treatment phases separated by 2-wk rest periods: two placebo phases; 0.3, 1.0, and 3.0 mg · kg−1 · day−1 pioglitazone hydrochloride phases; and a final placebo phase. During the second week of each treatment phase, serum insulin (immunoreactive insulin [IRI]), plasma glucose, and serum triglyceride (TG) levels were measured after an overnight fast and after a standardized meal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal tests. Pioglitazone hydrochloride significantly improved fasting and postprandial levels of IRI, plasma glucose, and TG in a dose-related manner (P < 0.05). Fasting values during treatment with 3.0 mg · kg−1 · day−1 were reduced by 64% for IRI, 19% for plasma glucose, and 44% for TG compared with the placebo phase before treatment. Efficacy of pioglitazone hydrochloride was more marked for those animals with fasting hyperglycemia. Insulin sensitivity was increased by pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose disappearance rate were not detectably affected. Systolic and mean arterial blood pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05). No toxic side effects of pioglitazone hydrochloride treatment were noted.

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