title: Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial.
abstract: To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug.
  
  
  
  After a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m2) were randomly assigned 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 insulin dose of 60 units/day, or to once-daily Lixi (20 μg/day) while continuing with metformin. The primary outcome was HbA1cchange at 30 weeks.
  
  
  
  Greater reductions in HbA1cfrom baseline (8.1% [65 mmol/mol]) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA1clevels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA1c<7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (-0.3 kg) and Lixi (-2.3 kg) and increased with iGlar (+1.1 kg, difference 1.4 kg, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was similar with iGlarLixi and iGlar (1.4 and 1.2 events/patient-year) and lower with Lixi (0.3 events/patient-year). iGlarLixi improved postprandial glycemic control versus iGlar and demonstrated considerably fewer nausea (9.6%) and vomiting (3.2%) events than Lixi (24% and 6.4%, respectively).
  
  
  
  iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA1creductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.
authors.affiliation: Dallas Diabetes Research Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: LMC Diabetes & Endocrinology, Toronto, Ontario, Canada.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Aronson
authors.affiliation: Grunberger Diabetes Institute, Bloomfield Hills, MI.
authors.forename: George
authors.initials: G
authors.lastname: Grunberger
authors.affiliation: GWT-TUD GmbH, Dresden Technical University, Dresden, Germany.
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: PierMarco
authors.initials: P
authors.lastname: Piatti
authors.affiliation: Groupe Hospitalier Mutualiste Les Portes du Sud, Vénissieux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Serusclat
authors.affiliation: Sanofi R&D, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Sanofi, Bridgewater, NJ.
authors.forename: Tianyue
authors.initials: T
authors.lastname: Zhou
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: Diabetes Research Centre, University of Leicester, Leicester, U.K.
authors.forename: Melanie
authors.initials: M
authors.lastname: Davies
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004338:Drug Combinations; D023381:Endpoint Determination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / 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*; D019518:Postprandial Period; D016896:Treatment Outcome; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D008687:Metformin; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor