title: Effect of exenatide, sitagliptin, or glimepiride on β-cell secretory capacity in early type 2 diabetes.
abstract: OBJECTIVE
  Agents that augment GLP-1 effects enhance glucose-dependent β-cell insulin production and secretion and thus are hoped to prevent progressive impairment in insulin secretion characteristic of type 2 diabetes (T2D). The purpose of this study was to evaluate GLP-1 effects on β-cell secretory capacity, an in vivo measure of functional β-cell mass, early in the course of T2D.
  
  
  METHODS
  We conducted a randomized controlled trial in 40 subjects with early T2D who received the GLP-1 analog exenatide (n = 14), the dipeptidyl peptidase IV inhibitor sitagliptin (n = 12), or the sulfonylurea glimepiride (n = 14) as an active comparator insulin secretagogue for 6 months. Acute insulin responses to arginine (AIRarg) were measured at baseline and after 6 months of treatment with 5 days of drug washout under fasting, 230 mg/dL (glucose potentiation of arginine-induced insulin release [AIRpot]), and 340 mg/dL (maximum arginine-induced insulin release [AIRmax]) hyperglycemic clamp conditions, in which AIRmax provides the β-cell secretory capacity.
  
  
  RESULTS
  The change in AIRpot was significantly greater with glimepiride versus exenatide treatment (P < 0.05), and a similar trend was notable for the change in AIRmax (P = 0.1). Within each group, the primary outcome measure, AIRmax, was unchanged after 6 months of treatment with exenatide or sitagliptin compared with baseline but was increased with glimepiride (P < 0.05). α-Cell glucagon secretion (AGRmin) was also increased with glimepiride treatment (P < 0.05), and the change in AGRmin trended higher with glimepiride than with exenatide (P = 0.06).
  
  
  CONCLUSIONS
  After 6 months of treatment, exenatide or sitagliptin had no significant effect on functional β-cell mass as measured by β-cell secretory capacity, whereas glimepiride appeared to enhance β- and α-cell secretion.
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Lalitha
authors: L
authors: Gudipaty
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Nora K
authors: NK
authors: Rosenfeld
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Carissa S
authors: CS
authors: Fuller
authors: Department of Mathematics, West Chester University of Pennsylvania, West Chester, PA.
authors: Robert
authors: R
authors: Gallop
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Mark H
authors: MH
authors: Schutta
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA rickels@mail.med.upenn.edu.
authors: Michael R
authors: MR
authors: Rickels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D050416:Glucagon-Secreting Cells / Q000187:drug effects*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D011719:Pyrazines; D013453:Sulfonylurea Compounds; D014230:Triazoles; D014688:Venoms; C057619:glimepiride; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000068900:Sitagliptin Phosphate