IMPROVEMENT IN GLUCOSE-TOLERANCE AND INSULIN-RESISTANCE IN OBESE SUBJECTS TREATED WITH TROGLITAZONE

Background. Troglitazone decreases insulin resistance and hyperglycemi a in patients with non-insulin-dependent diabetes mellitus (NIDDM), bu t its effects on subjects without diabetes are not known. Methods. We performed oral and intravenous glucose-tolerance tests, studies with t he euglycemic-hyperinsulinemic clamp, meal-tolerance tests, acid 24-ho ur blood-pressure measurements at base line and after the administrati on of troglitazone, 200 mg orally twice daily, or placebo for 12 weeks in 18 nondiabetic obese subjects, 9 of whom had impaired glucose tole rance. Results. The mean (+/-SD) rates of glucose disposal increased f rom 4.7+/-1.7 to 6.0+/-1.7 mg per kilogram of body weight per minute ( P = 0.004) and from 9.0+/-1.8 to 9.9+/-1.3 mg per kilogram per minute (P = 0.02) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute, respectively, in the troglitazone gro up. The insulin-sensitivity index, calculated from the results of intr avenous glucose-tolerance tests, increased from 0.7+/-0.6 x 10(-4) to 1.6+/-0.9 x 10(-4) in subjects given troglitazone, and their glycemic response to oral glucose and to mixed meals decreased. The mean fastin g plasma insulin concentration decreased by 48 percent (P = 0.002), an d the plasma insulin response to oral glucose and mixed meals decrease d by 40 and 41 percent, respectively. The changes were similar in the subjects with normal glucose tolerance and those with impaired glucose tolerance. Systolic and diastolic blood pressure decreased by 5+/-2 m m Hg (P = 0.05) and 4+/-2 mm Hg (P = 0.04), respectively, after treatm ent with troglitazone. There were virtually no changes in the placebo group. Conclusions. Troglitazone decreases insulin resistance and impr oves glucose tolerance in obese subjects with either impaired or norma l glucose tolerance. The ability of troglitazone to reduce insulin res istance could be useful in preventing NIDDM.