title: Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial.
abstract: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents.
  
  
  
  After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1clevels at 30 weeks.
  
  
  
  HbA1cdecreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1cfrom baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1cof 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c<7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi.
  
  
  
  Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.
authors.affiliation: Medstar Health Research Institute, Hyattsville, MD vanita.aroda@medstar.net.
authors.forename: Vanita R
authors.initials: VR
authors.lastname: Aroda
authors.affiliation: Dallas Diabetes Research Center at Medical City, Dallas, TX.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Rockwood Clinic, Spokane, WA.
authors.forename: Carol
authors.initials: C
authors.lastname: Wysham
authors.affiliation: Catalina Research Institute, Chino, CA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Unger
authors.affiliation: Complejo Hospitalario Universitario de Ferrol, A Coruña University, A Coruña, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Bellido
authors.affiliation: Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C., Universidad de Guadalajara, Hospital Civil de Guadalajara "Dr. Juan I. Menchaca," Guadalajara, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: González-Gálvez
authors.affiliation: Sanofi, Tokyo, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Takami
authors.affiliation: Biostatistics, BMD Consulting Inc., Somerset, NJ.
authors.forename: Hailing
authors.initials: H
authors.lastname: Guo
authors.affiliation: Diabetes Division, Sanofi, Frankfurt, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Niemoeller
authors.affiliation: Diabetes Division, Sanofi, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Souhami
authors.affiliation: International Diabetes Center, Park Nicollet Health Services, Minneapolis, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D023381:Endpoint Determination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D008687:Metformin; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor