title: Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial.
abstract: OBJECTIVE
  Patients with Type 1 diabetes have significantly elevated postprandial glucagon secretion. Dipeptidyl peptidase IV inhibitors improve HbA(1c) by several mechanisms, including increasing glucagon-like peptide 1 and glucose-dependent insulinotropic peptide concentrations, which decreases postprandial rises in glucagon in both Type 1 and Type 2 diabetes. This study evaluates the clinical implications of sitagliptin in adult patients with Type 1 diabetes.
  
  
  METHODS
  This investigator-initiated, double-blind, randomized, crossover, 8-week, pilot study enrolled 20 adult subjects with Type 1 diabetes. Subjects received sitagliptin 100 mg/day or placebo for 4 weeks and then crossed over. Outcomes included 2-h postprandial blood glucose and 24-h area under the curve changes in glucose measurements from continuous glucose monitoring, HbA(1c) , fructosamine and insulin dose.
  
  
  RESULTS
  Sitagliptin significantly reduced blood glucose (2-h postprandial and 24-h area under the curve) despite reduced total and prandial insulin dose. Based on continuous glucose monitor findings, sitagliptin improved measures of glycaemic control, including mean blood glucose (-0.6 mmol/l; P = 0.012) and time in euglycaemic range 4.4-7.8 mmol/l (0.4 ± 0.2 h; P = 0.046). Significant reductions were also observed in M100, Glycemic Risk Assessment Diabetes Equation (GRADE) and J-index. After controlling for period, treatment and insulin dose, the HbA(1c) was also significantly reduced [-0.27 ± 0.11% (-2.91 ± 1.16 mmol/mol); P = 0.025] when patients were taking sitagliptin.
  
  
  CONCLUSIONS
  Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Ellis
authors.forename: E G
authors.initials: EG
authors.lastname: Moser
authors.forename: J K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: A S
authors.initials: AS
authors.lastname: Rodionova
authors.forename: R M
authors.initials: RM
authors.lastname: Hazenfield
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010865:Pilot Projects; D019518:Postprandial Period; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014481:United States / Q000453:epidemiology
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles