We evaluated the efficacy of a thiazolidinedione in the treatment of diabetes induced by glucocorticoids. We examined the effectiveness of troglitazone in seven patients with long-standing steroid-induced diabetes. Five of the seven subjects were treated with insulin alone, one was treated with both insulin and oral therapy and one was treated with oral therapy alone. The mean insulin dose in six of the seven subjects was 0.66±0.09 units/kg per day. Diabetes status was assessed by measuring serum fructosamine, HgbA1c, oral glucose and meal tolerance tests (OGTT and MTT) at baseline and after treatment for 5-8 weeks with troglitazone 400 mg/day. Troglitazone caused a significant decrease in fructosamine (274±32 vs. 217±22 mmol/l; P<0.01) and HgbA1C (7.8±0.4 vs. 7.2±0.4%; P<0.01) as well as decrements in the areas under the OGTT 2,308±156 vs. 1,937±127 mmol/l; P<0.05) and MTT glucose curves (4694±449 vs. 4057±437 mmol/l; P<0.05). In addition, the area under the insulin curve for the oral glucose tolerance test showed a significant increase from 27,438±4,488 to 41,946±6,048 pmol/l (P<0.05). Total and LDL cholesterol were also significantly decreased (6.4±0.9 vs. 5.0±0.6 mmol/l and 3.8±0.7 vs. 2.7±0.4 mmol/l, respectively, P<0.05). Fasting leptin values decreased by 23% despite an increase in body weight. Troglitazone is effective in the treatment of glucocorticoid-induced diabetes as manifested by lower measures of glycemia, HgbA1c, and post-prandial glucose values, while the doses of other diabetes medications remained unchanged or were reduced. The insulin-sensitizing drug also produced a marked increase in endogenous insulin secretion in response to glucose, lower total and LDL cholesterol, and decreased fasting leptin despite weight gain. Thiazolidinediones may improve diabetes-related parameters by antagonizing pathways of glucocorticoid-induced insulin resistance and by reversing adverse effects of glucocorticoids on beta cell function. © 2002 Elsevier Science Ireland Ltd. All rights reserved.