title: Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes.
abstract: OBJECTIVE
  To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone.
  
  
  METHODS
  A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation.
  
  
  RESULTS
  Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.
  
  
  CONCLUSIONS
  Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@unipv.it
authors.forename: G
authors.initials: G
authors.lastname: Derosa
authors.forename: I G
authors.initials: IG
authors.lastname: Franzetti
authors.forename: F
authors.initials: F
authors.lastname: Querci
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: L
authors.initials: L
authors.lastname: Ciccarelli
authors.forename: M N
authors.initials: MN
authors.lastname: Piccinni
authors.forename: E
authors.initials: E
authors.lastname: Fogari
authors.forename: P
authors.initials: P
authors.lastname: Maffioli
mesh_terms: D052242:Adiponectin / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005215:Fasting / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007558:Italy / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014688:Venoms / Q000008:administration & dosage* / Q000494:pharmacology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; D008687:Metformin; D000077270:Exenatide