title: Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes.
abstract: OBJECTIVE
  We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure.
  
  
  METHODS
  Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and β-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI).
  
  
  RESULTS
  At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectively; P = 0.028).
  
  
  CONCLUSIONS
  EXE and GLAR sustained HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on β-cell health.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands. mcmbunck@vumc.nl
authors.forename: Mathijs C
authors.initials: MC
authors.lastname: Bunck
authors.forename: Anja
authors.initials: A
authors.lastname: Cornér
authors.forename: Bjorn
authors.initials: B
authors.lastname: Eliasson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Rimma M
authors.initials: RM
authors.lastname: Shaginian
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D010455:Peptides; D014688:Venoms