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Metformin plus low-dose glimeperide significantly improves homeostasis model assessment for insulin resistance (HOMA<inf>IR</inf>) and β-cell function (HOMA<inf>β-cell</inf>) without hyperinsulinemia in patients with type 2 diabetes mellitus

Abstract:

OBJECTIVE: Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic β-cells, which have been studied by using euglycemic/hyperinsulinemic clamps. However, it is difficult to study insulin resistance and β-cell failure by these techniques in humans. Therefore, the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and β-cell activity by using a mathematical model, Homeostasis Model Assessment for insulin resistance (HOMAIR) and β-cell function (HOMAβ-cell). RESEARCH DESIGN AND METHODS: Seventy type 2 diabetic patients were randomly assigned to one of three therapeutic regimens: (A) metformin + American Diabetic Association (ADA)-recommended diet + physical activity; (B) metformin + low-dose glimepiride + ADA diet + physical activity; or (C) ADA diet + physical activity (no drugs). Blood samples were obtained before and after the treatment to determine serum levels of fasting and post-prandial blood glucose, fasting insulin, and glycosylated hemoglobin (HbA1c), and HOMAIR and HOMAβ-cell were calculated. RESULTS: Fasting and post-prandial levels of glucose, HbA1c, and fasting insulin and calculated HOMAIR and HOMAβ-cell values before treatment were significantly higher than the respective values after treatment for all groups of patients (P < 0.01). Significant differences were also found when comparing the treatment-induced reduction in fasting blood glucose (51.8%; P < 0.01), post-prandial blood glucose (55.0%; P < 0.05), and HOMAIR (65.3%; P < 0.01) in patients of Group B with that in patients receiving other therapeutic options (Groups A and C). CONCLUSIONS: Metformin plus low-dose glimepiride (plus ADA diet and physical activity) is a more effective treatment for type 2 diabetes than either metformin plus ADA diet and physical activity or ADA diet and physical activity alone. Determination of HOMAIR and HOMAβ-cell values is an inexpensive, reliable, less invasive, and less labor-intensive method than other tests to estimate insulin resistance and β-cell function in patients with type 2 diabetes mellitus. © 2007 Lippincott Williams & Wilkins, Inc.