Glimepiride Improves Both First and Second Phases of Insulin Secretion in Type 2 Diabetes
- Mary Korytkowski, MD1,
- Abraham Thomas, MD2,
- Lynn Reid, CRNP3,
- Mary Beth Tedesco, CRNP1,
- William E. Gooding, PHD4 and
- John Gerich, MD5
- 1Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- 2Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- 3Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania
- 4Pittsburgh Cancer Institute Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
- 5Department 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
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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 2002.
M.K. is on the Speaker’s Bureau for Aventis and is a coinvestigator on an educational grant from Aventis to the University of Pittsburgh Center for Continuing Education. J.G. has received honoraria for speaking engagements, consulting fees, and research support from Novartis, Novo Nordisk, GlaxoSmithKline, Aventis, Bristol-Myers Squibb, and Pfizer, as well as consulting fees from Emisphere Pharmaceuticals.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
