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 carbo hydrate and lipid metabolism in patients with non-insulin-dependent di abetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 ye ar, 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 tria l from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulin emic (insulin infusion rate 9 mu moles.kg(-1).min(-1)) clamp studies m ere 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) l evel 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) l evel from 9.2 +/- 1.8% to 8.3 +/- 1.5%. Fasting serum insulin and C pe ptide. levels decreased from 83 +/- 36 pmol/liter and 0.62 +/- 0.21 nm ol/liter to 66 +/- 29 pmol/liter and 0.58 +/- 0.25 nmol/liter, respect ively. Fasting serum triglyceride and free fatty acids levels signific antly decreased with concomitant increase of fasting serum HDL-cholest erol levels from 1.2 +/- 0.2 to 1.5 +/- 0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated wit h baseline values of FPG (rho = 0.633), serum insulin (rho = 0.653), B MI (rho = 0,456), Rd (rho = -0.588) and 1,5-AG (rho=-0.522). These dat a indicate that pioglitazone enhances the insulin action in NIDDM pati ents on diet alone or SU, and thereby improves both plasma glucose lev el and lipid profiles. (C) 1997 Tohoku University Medical Press.