title: Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.
abstract: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins.
  
  
  
  MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies.
  
  
  
  Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted.
  
  
  
  Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Medicine, Duke University Medical Center at the Southern Regional Area Health Education Center (AHEC), Fayetteville, North Carolina.|Department of Community and Family Medicine, Duke University Medical Center at the Southern Regional Area Health Education Center (AHEC), Fayetteville, North Carolina.
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Wright
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana.
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Kwan
authors.affiliation: ICON Epidemiology, Vancouver, British Columbia, Canada.
authors.forename: Juliette C
authors.initials: JC
authors.lastname: Thompson
authors.affiliation: ICON Epidemiology, Vancouver, British Columbia, Canada.
authors.forename: Iqra A
authors.initials: IA
authors.lastname: Syed
authors.affiliation: ICON Epidemiology, Vancouver, British Columbia, Canada.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Korol
authors.affiliation: ICON Epidemiology, Vancouver, British Columbia, Canada.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Waser
authors.affiliation: Eli Lilly Canada Inc., Toronto, Ontario, Canada.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Yu
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana.
authors.forename: Rattan
authors.initials: R
authors.lastname: Juneja
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage; D054795:Incretins / Q000008:administration & dosage*; D007328:Insulin / Q000627:therapeutic use*; D000069057:Insulin Detemir / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D000069450:Liraglutide / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D014688:Venoms / Q000008:administration & dosage; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D054795:Incretins; D007328:Insulin; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D000069450:Liraglutide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human; C571886:insulin degludec; C555680:dulaglutide
keywords: 
  GLP-1 RAs; basal insulin; glycaemic control; meta-analysis; systematic review; type 2 diabetes