title: Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial.
abstract: OBJECTIVE
  This mechanistic trial compared the pharmacodynamics and safety of lixisenatide and liraglutide in combination with optimized insulin glargine with/without metformin in type 2 diabetes (T2D).
  
  
  METHODS
  This was a multicenter, randomized, open-label, three-arm trial comparing lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg once daily for 8 weeks in combination with insulin glargine after optimized titration. The primary end point was change from baseline to week 8 in incremental area under the postprandial plasma glucose curve for 4 h after a standardized solid breakfast (AUC PPG0030-0430 h). Changes from baseline in gastric emptying, 24-h plasma glucose profile, HbA1c, fasting plasma glucose (FPG), 24-h ambulatory heart rate and blood pressure, amylase and lipase levels, and adverse events (AEs) were also assessed.
  
  
  RESULTS
  In total, 142 patients were randomized and treated. Lixisenatide 20 µg achieved greater reductions of AUC PPG0030-0430 h compared with liraglutide (marginal mean [95% one-sided CI] treatment difference, -6.0 [-7.8] h ⋅ mmol/L [-108.3 (-140.0) h ⋅ mg/dL] vs. liraglutide 1.2 mg and -4.6 [-6.3] h ⋅ mmol/L [-83.0 (-114.2) h ⋅ mg/dL] vs. liraglutide 1.8 mg; P < 0.001 for both), and gastric emptying was delayed to a greater extent than with liraglutide 1.2 and 1.8 mg (P < 0.001 for treatment comparisons). FPG was unchanged in all treatment arms. At week 8, mean ± SD HbA1c was 6.2 ± 0.4% (44 ± 5 mmol/mol), 6.1 ± 0.3% (44 ± 4 mmol/mol), and 6.1 ± 0.3% (44 ± 4 mmol/mol) for lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg, respectively. At week 8, both liraglutide doses increased marginal mean ± SE 24-h heart rate from baseline by 9 ± 1 bpm vs. 3 ± 1 bpm with lixisenatide (P < 0.001). Occurrence of symptomatic hypoglycemia was higher with lixisenatide; gastrointestinal AEs were more common with liraglutide. Lipase levels were significantly increased from baseline with liraglutide 1.2 and 1.8 mg (marginal mean ± SE increase 21 ± 7 IU/L for both; P < 0.05).
  
  
  CONCLUSIONS
  Lixisenatide and liraglutide improved glycemic control in optimized insulin glargine-treated T2D albeit with contrasting mechanisms of action and differing safety profiles.
authors.affiliation: Diabetes Division, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany juris.meier@rub.de.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Sanofi R&D, Chilly-Mazarin, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Hincelin-Méry
authors.affiliation: Sanofi R&D, Chilly-Mazarin, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Roy-Duval
authors.affiliation: Sanofi R&D, Chilly-Mazarin, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Delfolie
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Hans-Veit
authors.initials: HV
authors.lastname: Coester
authors.affiliation: Diabetes Division, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Bjoern A
authors.initials: BA
authors.lastname: Menge
authors.affiliation: Profil, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage; D000069450:Liraglutide / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D019518:Postprandial Period / Q000187:drug effects; D016896:Treatment Outcome; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D000069450:Liraglutide; D008687:Metformin; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor