title: Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon counterregulation during hypoglycemia in type 1 diabetes.
abstract: BACKGROUND
  The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.
  
  
  OBJECTIVE
  The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).
  
  
  METHODS
  The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.
  
  
  METHODS
  The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured.
  
  
  RESULTS
  During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4±0.2 vs. 2.6±0.2 nmol/liter×minutes, P=0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5±1.0 pmol/liter with vildagliptin vs. 1.7±0.8 pmol/liter with placebo, P=NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4±1.0 mmol/mol (-0.32±0.09%; P=0.002)] from baseline of 57.9 mmol/mol (7.5%).
  
  
  CONCLUSIONS
  Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.
authors.affiliation: Department of Clinical Sciences, Lund University, B11 BMC, SE-221 84 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Farngren
authors.forename: Margaretha
authors.initials: M
authors.lastname: Persson
authors.forename: Anja
authors.initials: A
authors.lastname: Schweizer
authors.forename: James E
authors.initials: JE
authors.lastname: Foley
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000097:blood*; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D000077597:Vildagliptin; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D005934:Glucagon; D000077597:Vildagliptin; D000218:Adamantane