The aim of the study was to compare the long-term effect of 4
antidiabetic treatment protocols on
insulin resistance evaluated by euglycemic hyperinsulinemic clamp in
type 2 diabetes mellitus patients. Two hundred seventy-one
type 2 diabetes mellitus patients with poor
glycemic control and who were
overweight were enrolled in this study. Patients were randomized and titrated to take
pioglitazone,
metformin,
pioglitazone +
metformin, or
glimepiride +
metformin for 15 months. They underwent a euglycemic hyperinsulinemic clamp at baseline, after 3 months, and after 15 months. Anthropometric and metabolic measurements were assessed at baseline, after 3 months, and after 15 months. There was a decrease in
glycated hemoglobin in all groups, but
glycated hemoglobin value was lower in the group treated with
pioglitazone +
metformin compared with the groups treated with
metformin alone and with
pioglitazone alone. There was a decrease in fasting plasma
glucose and postprandial plasma
glucose values in all groups, but values obtained with
pioglitazone +
metformin were lower compared with values in the groups treated with
metformin alone and with
pioglitazone alone. Fasting plasma
insulin and postprandial plasma
insulin values were higher in the group treated with
glimepiride +
metformin compared with the other groups. After 15 months,
glucose infusion rate and total
glucose requirement values observed in the groups treated with
pioglitazone alone and with
pioglitazone +
metformin were higher compared with the values in the group treated with
metformin alone and with
glimepiride +
metformin; furthermore, values obtained in the group treated with
pioglitazone +
metformin were higher than the value obtained with
pioglitazone alone.
Pioglitazone-
metformin-based therapeutic control is associated with the most quantitatively relevant improvement in
insulin resistance-related parameters, whereas the sulfonylurea-
metformin-including protocol has less relevant effects.