title: Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial.
abstract: OBJECTIVE
  Traditional blood glucose lowering agents do not prevent the progressive loss of beta cell function in patients with type 2 diabetes. The dipeptidylpeptidase (DPP)-4 inhibitor vildagliptin improves beta cell function both acutely and chronically (up to 2 years). Whether this effect persists after cessation of treatment remains unknown. Here, we assessed the insulin secretory capacity in drug-naive patients with type 2 diabetes after a 52 week treatment period with vildagliptin or placebo, and again after a 12 week washout period.
  
  
  METHODS
  This study was conducted at a single university medical centre, and was a double-blind, randomised clinical trial in 59 drug-naive patients with type 2 diabetes and mild hyperglycaemia to either vildagliptin 100 mg (n = 29) or placebo (n = 30). Randomisation was performed by a validated 1:1 system. Neither patient, nor caregiver, was informed about the assigned treatment. Inclusion criteria were drug-naive patients ≥30 years, with HbA(1c) ≤7.5% and BMI of 22-45 kg/m(2). The mildly hyperglycaemic patient population was chosen to minimise glucose toxicity as a confounding variable. Beta-cell function was measured during an arginine-stimulated hyperglycaemic clamp at week 0, week 52 and after a 12 week washout period. All patients with at least one post-randomisation measure were analysed (intent-to-treat).
  
  
  RESULTS
  Fifty-two week vildagliptin 100 mg (n = 26) treatment increased the primary efficacy variable, combined hyperglycaemia and arginine-stimulated C-peptide secretion (AIR(arg)), by 5.0 ± 1.8 nmol/l × min, while it decreased by 0.8 ± 1.8 nmol/l × min with placebo (n = 25) (between-group difference p = 0.030). No significant between-group difference in AIR(arg) was seen after the 12 week washout period. The between-group difference adjusted mean 52 week changes from baseline was -0.19 ± 0.11, p = 0.098 and -0.22 ± 0.23%, p = 0.343 for HbA(1c) and fasting plasma glucose, respectively. There were no suspected drug treatment-related serious adverse events.
  
  
  CONCLUSIONS
  One year treatment with vildagliptin significantly increased beta cell secretory capacity. This effect was not maintained after the washout, indicating that this increased capacity was not a disease modifying effect on beta cell mass and/or function.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00260156.
authors.affiliation: Novartis Pharmaceutical Cooperation, Clinical Research and Development, One Health Plaza, East Hanover, NJ 07936, USA. james.foley@novartis.com
authors.forename: J E
authors.initials: JE
authors.lastname: Foley
authors.forename: M C
authors.initials: MC
authors.lastname: Bunck
authors.forename: D L
authors.initials: DL
authors.lastname: Möller-Goede
authors.forename: M
authors.initials: M
authors.lastname: Poelma
authors.forename: G
authors.initials: G
authors.lastname: Nijpels
authors.forename: E M
authors.initials: EM
authors.lastname: Eekhoff
authors.forename: A
authors.initials: A
authors.lastname: Schweizer
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
authors.forename: M
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin