A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients

Troglitazone and metformin lower glucose levels in diabetic patients withou t increasing plasma insulin levels. We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin s ecretion in 20 type 2 diabetic patients. To avoid the confounding effect of improved glycemic control on insulin action and secretion, patients were f irst rendered euglycemic with 4 weeks of continuous subcutaneous insulin in fusion (CSII) before randomization to CSII plus troglitazone (n = 10) or CS II pins metformin (n = 10); euglycemia was maintained for another 6-7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline, 2) after 4 weeks of CSII, and 3) after CSII plus either trog litazone or metformin, The 24-h glucose, insulin, and C-peptide profiles we re performed on the day before the second and third glucose clamps. Good gl ycemic control was achieved with CSII alone and was maintained with CSII pl us an oral agent (mean 24-h glucose: troglitazone, 6.2 +/- 0.6 mmol/l; metf ormin, 6.2 +/- 0.3 mmol/l). Insulin requirements decreased 53% with troglit azone compared with CSII alone (48 +/- 4 vs. 102 +/- 13 U/day, P < 0.001), but only 31% with metformin (76 +/- 13 vs. 110 +/- 18 U/day, P < 0.005). Th e 24-h C-peptide profiles were similar. Normal fasting hepatic glutose outp ut was maintained with both agents despite lower insulin levels than on CSI I alone. insulin sensitivity did not change significantly with CSII alone o r with CSII pins metformin, but improved 29% with CSII plus troglitazone (P < 0.005 vs, CSII alone) and was then 45% higher than in the CSII plus metf ormin patients (P < 0.005). In conclusion, metformin has no effect on insul in-stimulated glucose disposal independent of glycemic control in type 2 di abetes, Troglitazone (600 mg/day) has greater insulin-sparing effects than metformin (1,700 mg/day) in CSII-treated euglycemic patients. This is proba bly explained by the peripheral tissue insulin-sensitizing effects of trogl itazone.