Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM

We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index [BMI] 23.9 +/- 3.4 kg/m(2) [mean +/- S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 mu moles.kg(-1).min(-1)) clamp studies mere performed before and after oral administration of pioglitazone (30 mg/day) for 87 +/- 10 days. The Rd significantly improved from 5.5 +/- 2.5 to 8.3 +/- 3.1 mg.kg(-1).min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0 +/- 2.0.mmol/liter to 8.9 +/- 1.1 mmol/liter with a significant improvement in the hemoglobin A(1c) level from 9.2 +/- 1.8% to 8.3 +/- 1.5%. Fasting serum insulin and C peptide. levels decreased from 83 +/- 36 pmol/liter and 0.62 +/- 0.21 nmol/liter to 66 +/- 29 pmol/liter and 0.58 +/- 0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2 +/- 0.2 to 1.5 +/- 0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho = 0.633), serum insulin (rho = 0.653), BMI (rho = 0,456), Rd (rho = -0.588) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles. (C) 1997 Tohoku University Medical Press.