title: A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus.
abstract: BACKGROUND
  Liraglutide, a human glucagon-like peptide 1 (GLP-1) analogue that has received marketing approval from the European Commission, is a treatment for type 2 diabetes mellitus (DM) that is administered as a once-daily subcutaneous injection.
  
  
  OBJECTIVE
  The aim of this review was to summarize the efficacy and safety data published about liraglutide, focusing on data from Phase III clinical trials.
  
  
  METHODS
  Relevant English-language publications were identified through a search of MEDLINE and EMBASE (from 1948 to October 2009). The search terms included the following: GLP-1, incretin effect, liraglutide, NN2211, exenatide, sitagliptin, and vildagliptin. Original research papers about liraglutide that were published in peer-reviewed journals were considered.
  
  
  RESULTS
  The literature search identified 39 relevant publications. The efficacy and tolerability of oncedaily liraglutide at doses of 0.6, 1.2, and 1.8 mg for type 2 DM, in combination with, and compared with, other type 2 DM treatments were investigated in the Liraglutide Effect and Action in Diabetes (LEAD) Phase III clinical trial program. In the LEAD studies, consistent reductions in glycosylated hemoglobin (HbA(1c)) of up to 1.6% were seen with liraglutide, and up to 66% of patients achieved the HbA(1c) goal of <7%. Fasting and postprandial plasma glucose levels were also consistently reduced across the LEAD trials by up to 43 mg/dL (2.4 mmol/L) and 49 mg/dL (2.7 mmol/L), respectively. Hypoglycemia was reported at a rate of 0.03 to 1.9 events per patient annually. Liraglutide significantly improved beta-cell function, as measured by homeostasis model assessment for beta-cell function analysis (20%-44%) and by ratios of pro-insulin to insulin (-0.11 to 0.01). Consistent reductions in systolic blood pressure up to 6.7 mm Hg were also observed for liraglutide treatment. Liraglutide treatment, as monotherapy and in combination with oral antidiabetic drugs (OADs), was associated with weight loss of up to 3.24 kg. Overall, liraglutide was well tolerated. Nausea was the most common adverse event observed with liraglutide treatment, reported by 5% to 29% of patients; however, nausea was generally mild and transient.
  
  
  CONCLUSIONS
  Once-daily liraglutide was effective and well tolerated when used as monotherapy or in combination with OADs in patients with type 2 DM, and is therefore a promising new treatment option for the management of type 2 DM.
authors.affiliation: Endocrine Unit, University Hospital of Bellvitge, Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain. montanya@ub.edu
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D000069450:Liraglutide; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D054795:Incretins; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1