title: Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L).
abstract: OBJECTIVE
  To examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA1c).
  
  
  METHODS
  We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA1c reduction from baseline was the primary end point.
  
  
  RESULTS
  Mean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA1c from baseline was -0.4% (95% CI -0.6 to -0.2; P = 0.0002), and mean HbA1c at end point was 7.8%. HbA1c <7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P < 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, -3.8 mmol/L; P < 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, -1.3 kg; P < 0.0001) and insulin dosage (-3.7 units/day; P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo.
  
  
  CONCLUSIONS
  By improving HbA1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.
authors.affiliation: Oregon Health & Science University, Portland, Oregon, USA. riddlem@ohsu.edu
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Riddle
authors.forename: Ronnie
authors.initials: R
authors.lastname: Aronson
authors.forename: Philip
authors.initials: P
authors.lastname: Home
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Niemoeller
authors.forename: Patrick
authors.initials: P
authors.lastname: Miossec
authors.forename: Lin
authors.initials: L
authors.lastname: Ping
authors.forename: Jenny
authors.initials: J
authors.lastname: Ye
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use*; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor