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

Glimepiride Improves Both First and Second Phases of Insulin Secretion in Type 2 Diabetes Mary Korytkowski , MD 1 , Abraham Thomas , MD 2 , Lynn Reid , CRNP 3 , Mary Beth Tedesco , CRNP 1 , William E. Gooding , PHD 4 and John Gerich , MD 5 1 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 2 Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 3 Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania 4 Pittsburgh Cancer Institute Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 5 Department of Medicine, University of Rochester, Rochester, New York 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. EGP, endogenous glucose production GCRC, General Clinical Research Center GIR, glucose infusion rate HOMA, homeostasis model assessment NDDG, National Diabetes Data Group SA, specific activity Footnotes Address correspondence and reprint requests to Mary Korytkowski, Falk, Room 588, 3601 Fifth Ave., Pittsburgh, PA 15213. E-mail: korytkowski{at}msx.dept-med.pitt.edu . Received for publication 2 April 2002 and accepted in revised form 12 June