title: Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S).
abstract: OBJECTIVE
  To assess efficacy and safety of lixisenatide once-daily versus placebo in type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU) ± metformin.
  
  
  METHODS
  In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24.
  
  
  RESULTS
  Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: -0.85% vs. -0.10%; p<0.0001) and more patients achieved HbA1c <7.0% (36.4% vs. 13.5%; p<0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: -111.48 vs. -3.80 mg/dL [-6.19 vs. -0.21 mmol/L]; p<0.0001) and glucose excursion (-94.11 vs. +6.24 mg/dL [-5.22 vs. +0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide.
  
  
  CONCLUSIONS
  Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA. Electronic address: JulioRosenstock@DallasDiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Centre for Clinical Studies, GWT-TUD GmbH, Dresden, Germany.
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.affiliation: Bangalore Diabetes Centre, Bangalore, India.
authors.forename: Paramesh
authors.initials: P
authors.lastname: Shamanna
authors.affiliation: Eulji General Hospital, Seoul, Republic of Korea.
authors.forename: Kyung Wan
authors.initials: KW
authors.lastname: Min
authors.affiliation: Sanofi R&D, Chilly-Mazarin, France.
authors.forename: Gabor
authors.initials: G
authors.lastname: Boka
authors.affiliation: Sanofi R&D, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Miossec
authors.affiliation: Sanofi, Bridgewater, NJ, USA.
authors.forename: Tianyue
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Sanofi R&D, Frankfurt, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Muehlen-Bartmer
authors.affiliation: Medstar Health Research Institute and Georgetown University Medical School, Washington, DC, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D038622:Internationality; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D019518:Postprandial Period; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010455:Peptides; D013453:Sulfonylurea Compounds; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: GLP-1 receptor agonists; Lixisenatide; Sulfonylurea; Type 2 diabetes