title: Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study.
abstract: OBJECTIVE
  To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2 years in patients with type 2 diabetes.
  
  
  METHODS
  In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n = 1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy ≥3 months), or 7.0-10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension.
  
  
  RESULTS
  HbA1c decreased significantly with liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg, respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001). Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time.
  
  
  CONCLUSIONS
  Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.
authors.affiliation: Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Bad Lauterberg, Germany. nauck@diabeteszentrum.de
authors.forename: M
authors.initials: M
authors.lastname: Nauck
authors.forename: A
authors.initials: A
authors.lastname: Frid
authors.forename: K
authors.initials: K
authors.lastname: Hermansen
authors.forename: A B
authors.initials: AB
authors.lastname: Thomsen
authors.forename: M
authors.initials: M
authors.lastname: During
authors.forename: N
authors.initials: N
authors.lastname: Shah
authors.forename: T
authors.initials: T
authors.lastname: Tankova
authors.forename: I
authors.initials: I
authors.lastname: Mitha
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / 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*; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride