The Effect of Rosiglitazone on the Liver: Decreased Gluconeogenesis in Patients with Type 2 Diabetes

Aims/Hypothesis: Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones have been shown to improve glycemic control and increase peripheral insulin sensitivity. Whether chronic thiazolidinedione treatment is associated with a decrease in GNG has not been determined. Materials and Methods: We studied 26 diet-treated type 2 diabetic patients randomly assigned to rosiglitazone (RSG; 8 mg/d; n = 13) or placebo (n = 13) for 12 wk. At baseline and 12 wk, we measured endogenous glucose production (by [3H]glucose infusion) and GNG (by the [2H]2O technique) after a 15-h fast. Peripheral insulin sensitivity was evaluated by a two-step (240 and 960 pmol/min/m-2) euglycemic insulin clamp. Results: Compared with placebo, RSG reduced fasting plasma glucose (9.7 ± 0.7 to 7.4 ± 0.3 mmol/liter; P 0.001), fasting fractional GNG (-15 ± 4%; P