title: Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme.
abstract: OBJECTIVE
  We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus (T2DM) treated with liraglutide versus comparator diabetes therapies.
  
  
  METHODS
  Twenty-six-week data from seven phase 3, randomized trials in the liraglutide T2DM development programme were analysed by trial and treatment group: liraglutide (1.2 and 1.8 mg), active comparator and placebo. Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline; impact of body mass index (BMI) and gastrointestinal (GI) adverse events (AEs) on weight change and correlation of weight change with change in glycosylated haemoglobin (HbA1c).
  
  
  RESULTS
  A number of subjects experienced >5% weight loss during the trials (24.4% liraglutide 1.8 mg and 17.7% liraglutide 1.2 mg; 17.7% exenatide, 10.0% sitagliptin, 3.6-7.0% sulphonylurea, 2.6% thiazolidinedione and 2.6% glargine; 9.9% placebo). More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide. Across trials, higher initial BMI was associated with slightly greater weight loss with liraglutide. Mean weight loss increased slightly the longer GI AEs persisted. Although HbA1c reduction was slightly larger in higher weight loss categories across treatments (including placebo), sample sizes were small and no clear correlation could be determined. Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced; thus, not all HbA1c-lowering effect appears weight mediated.
  
  
  CONCLUSIONS
  The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis. Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, USA. kevin.niswender@vanderbilt.edu
authors.forename: K
authors.initials: K
authors.lastname: Niswender
authors.forename: X
authors.initials: X
authors.lastname: Pi-Sunyer
authors.forename: J
authors.initials: J
authors.lastname: Buse
authors.forename: K H
authors.initials: KH
authors.lastname: Jensen
authors.forename: A D
authors.initials: AD
authors.lastname: Toft
authors.forename: D
authors.initials: D
authors.lastname: Russell-Jones
authors.forename: B
authors.initials: B
authors.lastname: Zinman
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D000069450:Liraglutide; D010455:Peptides; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014230:Triazoles; D014688:Venoms; C517652:hemoglobin A1c protein, human