title: Exenatide improves β-cell function up to 3 years of treatment in patients with type 2 diabetes: a randomised controlled trial.
abstract: OBJECTIVE
  Glucagon-like peptide (GLP)-1 receptor agonist treatment improves β-cell function. In this study, we investigated whether the improvements are sustained during a 3-year treatment period.
  
  
  METHODS
  Sixty-nine metformin-treated type 2 diabetes patients were randomised to the GLP1 receptor agonist, exenatide (EXE) twice daily (BID) or to insulin glargine (GLAR). β-cell function parameters were derived using the Mari model from standardised breakfast and lunch meals that were administered before treatment, and after 1 and 3 years of treatment. EXE was administered before breakfast.
  
  
  RESULTS
  Fifty-nine (EXE: n = 30; GLAR: n = 29) and thirty-six (EXE: n = 16; GLAR: n = 20) patients completed the meal at 1- and 3-year treatment respectively. After 3 years, groups had comparable glycaemic control (HbA1c: EXE 6.6 ± 0.2% and GLAR 6.9 ± 0.2%; P = 0.216). Compared with GLAR, at 1 and 3 years, EXE induced a stronger reduction in post-breakfast glucose concentrations (P < 0.001), with lower C-peptide levels (P < 0.001). Compared with GLAR, EXE increased insulin secretion at 8 mmol/L glucose throughout the study period (P < 0.01). Both treatments improved β-cell glucose sensitivity after 1-year treatment. However, only EXE treatment sustained this improvement for 3 years. No consistent changes in other β-cell parameters including rate sensitivity and potentiation were observed.
  
  
  CONCLUSIONS
  Compared with GLAR, EXE improved the parameters of β-cell function, especially insulin secretion at 8 mmol/L glucose and β-cell glucose sensitivity, which was sustained during the 3-year treatment period.
authors.affiliation: Diabetes CenterDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.affiliation: Diabetes CenterDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Eli Lilly and CompanyUtrecht, The Netherlands.
authors.forename: Mathijs C
authors.initials: MC
authors.lastname: Bunck
authors.affiliation: Diabetes CenterDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Department of Health Sciences and the EMGO Institute for Health and Care ResearchVU University Amsterdam, Amsterdam, The Netherlands Department of Epidemiology and BiostatisticsVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Research Programs' UnitDiabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Anja
authors.initials: A
authors.lastname: Cornér
authors.affiliation: Diabetes CenterDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Lundberg Laboratory for Diabetes ResearchSahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Eliasson
authors.affiliation: Research Programs' UnitDiabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.lastname: Marja-RiittaTaskinen
authors.affiliation: Diabetes CenterDepartment of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Eli Lilly and CompanyIndianapolis, Indiana, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.affiliation: Lundberg Laboratory for Diabetes ResearchSahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
authors.affiliation: Research Programs' UnitDiabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.lastname: HanneleYki-Järvinen
authors.affiliation: Institute of NeuroscienceNational Research Council, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
mesh_terms: D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D019518:Postprandial Period; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide