Glimepiride Improves Both First and Second Phases of Insulin Secretion in Type 2 Diabetes

Abstract

OBJECTIVE—The purpose of this study was to assess the effect of glimepiride on insulin sensitivity and secretion in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—After a 2-week washout from prior sulfonylurea therapy, 11 obese subjects with type 2 diabetes underwent euglycemic and hyperglycemic clamp studies before and during glimepiride therapy. RESULTS—Glimepiride resulted in a 2.4-mmol/l decrease in fasting plasma glucose (P = 0.04) that was correlated with reductions in postabsorptive endogenous glucose production (EGP) (16.4 ± 0.6 vs. 13.5 ± 0.5 μmol · kg−1 · min−1, P = 0.01) (r = 0.21, P = 0.01). Postabsorptive EGP on glimepiride was similar to that of control subjects (12.8 ± 0.9 μmol · kg−1 · min−1, NS). Fasting plasma insulin (66 ± 18 vs. 84 ± 48 pmol/l, P = 0.05), and first-phase (19 ± 8 vs. 32 ± 11 pmol/l, P = 0.04) and second-phase incremental insulin responses to glucose (48 ± 23 vs. 72 ± 32 pmol/l, P = 0.02) improved with glimepiride therapy. Insulin sensitivity did not change with treatment (4.6 ± 0.7 vs. 4.3 ± 0.7 μmol · kg−1 · min−1 · pmol−1) and remained below that of control subjects (8.1 ± 1.8 μmol · kg−1 · min−1 · pmol−1, P = 0.04). CONCLUSIONS—The current study demonstrates that glimepiride improves both first and second phases of insulin secretion, but not insulin sensitivity, in individuals with type 2 diabetes.