Glimepiride improves both first and second phases of insulin secretion in type 2 diabetes

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 mumol . 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 mumol kg(-1) . min(-1), NS). Fasting plasma insulin (66 +/- IS 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 mumol . kg(-1) . min(-1) . pmol(-1)) and remained below that of control subjects (8.1 +/- 1.8 mumol . 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.