Issue 123 Item 7 Glimepiride Improves Insulin Secretion, Not Insulin Sensitivity

Patients with impaired glucose tolerance (on the way to type 2 diabetes) might benefit from earlier treatment with glimepiride. Glimepiride, improves the first and second phases of insulin secretion, but not insulin sensitivity, in patients with type 2 diabetes, according to a report published in the September issue of Diabetes Care.

In animal studies, glimepiride treatment brought greater plasma glucose reductions per insulin level increment than did glyburide or glipizide, suggesting that its beneficial effects might include an improvement in insulin sensitivity, the authors explain.

Dr. Mary Korytkowski, from University of Pittsburgh, Pennsylvania, and colleagues studied the effects of glimepiride on insulin sensitivity and secretion using euglycemic and hyperglycemic clamp studies in 8 men and 3 women with type 2 diabetes and in 5 men and 2 women with normal glucose tolerance.

Fasting plasma glucose levels decreased and fasting plasma insulin levels increased in the diabetic subjects treated with glimepiride, despite the fact that they had already been receiving sulfonylurea treatment, the authors report.

Postabsorptive endogenous glucose production (EGP), which was higher in diabetic patients before glimepiride treatment, fell with glimepiride treatment to levels seen in the nondiabetic subjects, the results indicate.

During the hyperglycemic clamp studies, incremental first-phase and steady-state insulin secretion increased in the glimepiride-treated diabetic patients, the researchers note. "The observed improvement in first-phase insulin release…was unexpected since sulfonylureas are generally thought to only affect second-phase insulin release," the investigators observe.

Glimepiride therapy brought no improvement in any measure of insulin sensitivity, the report indicates.

These findings suggest "that there may be differences among agents in the sulfonylurea class," Dr. Korytkowski told Reuters Health. "Studies investigating first and second phase of insulin release with other sulfonylureas would be welcome."

It is theoretically possible that patients with impaired glucose tolerance (on the way to type 2 diabetes) might benefit from earlier treatment with glimepiride, Dr. Korytkowski also said.

"As reductions in first-phase insulin secretion are described in individuals at risk for type 2 diabetes, clinical trials of therapy targeting improvements in early insulin release as a means of preventing deterioration to type 2 diabetes may be warranted," the authors conclude. Diabetes Care 2002;25:1607-1611