title: Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira).
abstract: OBJECTIVE
  Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes.
  
  
  METHODS
  In a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86 mmol/mol]) on basal insulin (20-40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline.
  
  
  RESULTS
  A total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference -1.1% [95% CI -1.3, -0.8], -12 mmol/mol [95% CI -14, -9; P < 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%).
  
  
  CONCLUSIONS
  IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component.
authors.affiliation: University of North Carolina School of Medicine, Endocrinology & Metabolism, Chapel Hill, NC john_buse@med.unc.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: University of Copenhagen, Gentofte Hospital, Center for Diabetes Research, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Endocrinology, SSM Medical Group, St. Louis, MO.
authors.forename: Jerry
authors.initials: J
authors.lastname: Thurman
authors.affiliation: Texas Diabetes and Endocrinology, Austin, TX.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Blevins
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Irene H
authors.initials: IH
authors.lastname: Langbakke
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Bøttcher
authors.affiliation: Endocrine and Metabolic Consultants, Clinical Research, Rockville, MD.
authors.forename: Helena W
authors.initials: HW
authors.lastname: Rodbard
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; C571886:insulin degludec; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D008687:Metformin