title: Effects of lixisenatide once daily on gastric emptying in type 2 diabetes--relationship to postprandial glycemia.
abstract: OBJECTIVE
  To determine the effects of lixisenatide, a new once-daily (QD) glucagon-like peptide-1 receptor agonist, on postprandial glucose (PPG) and gastric emptying, and the relationship between these effects in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Data were obtained from a randomized, double-blind, placebo-controlled, parallel-group study with treatment duration of 28 days in patients with T2DM receiving ≤2 oral antidiabetic drugs. Lixisenatide was injected subcutaneously using an ascending dose range (5-20 μg) increased every fifth day in increments of 2.5 μg. Blood glucose was determined before and after three standardized meals (breakfast, lunch, and dinner). Gastric emptying of the standardized breakfast was determined by a (13)C-octanoic acid breath test at baseline (Day-1) and at Day 28.
  
  
  RESULTS
  A total of 21 and 22 patients were randomized to lixisenatide 20 μg QD and placebo, respectively. With lixisenatide 20 μg QD, there was a reduction in PPG when compared with placebo after breakfast (p<0.0001), lunch (p<0.001) and dinner (p<0.05). Hence, lixisenatide 20 μg administered in the morning exhibited a pharmacodynamic effect on blood glucose throughout the day. Gastric emptying (50% emptying time) increased substantially from baseline with lixisenatide 20 μg QD, but not with placebo (change from baseline ± SD: -24.1 ± 133.1 min for placebo and 211.5 ± 278.5 min for lixisenatide; p<0.01). There was an inverse relationship between PPG area under the curve after breakfast and gastric emptying with lixisenatide 20 μg QD (n=17, r(2)=0.51, p<0.05), but not with placebo.
  
  
  CONCLUSIONS
  In this study, lixisenatide at a dose of 20 μg QD reduced postprandial glycemic excursions in patients with T2DM, possibly as a result of sustained slowing of gastric emptying.
authors.affiliation: Sanofi, Frankfurt am Main, Germany. Electronic address: martin.lorenz@sanofi.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Lorenz
authors.forename: Claudia
authors.initials: C
authors.lastname: Pfeiffer
authors.forename: Axel
authors.initials: A
authors.lastname: Steinsträsser
authors.forename: Reinhard H A
authors.initials: RH
authors.lastname: Becker
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rütten
authors.forename: Peter
authors.initials: P
authors.lastname: Ruus
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D019518:Postprandial Period; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: Gastric emptying; Glucagon-like peptide-1 receptor agonist; Lixisenatide; Postprandial blood glucose; Type 2 diabetes