title: Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.
  
  
  METHODS
  This investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels.
  
  
  RESULTS
  There were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia.
  
  
  CONCLUSIONS
  Sitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation.
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center Aurora, Colorado Diabetes Technology and Therapeutics University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Satish.Garg@ucdenver.edu
authors.forename: Satish K
authors.initials: SK
authors.lastname: Garg
authors.forename: Emily G
authors.initials: EG
authors.lastname: Moser
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Bode
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Klaff
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.forename: Christie
authors.initials: C
authors.lastname: Beatson
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000068900:Sitagliptin Phosphate