title: Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis.
abstract: BACKGROUND
  Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide robust glucose-lowering capability with low risk of hypoglycaemia or weight gain. We thus did a systematic review and meta-analysis of randomised controlled trials to assess the effect of this combination treatment on glycaemic control, hypoglycaemia, and weight gain in patients with type 2 diabetes.
  
  
  METHODS
  We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov, and ClinicalTrials.gov for randomised controlled trials (published between Jan 1, 1950, and July 29, 2014; no language restrictions) comparing GLP-1 agonist and basal insulin combination treatment to other anti-diabetic treatments. Our main endpoints were glycaemic control, hypoglycaemia, and change in weight. We assessed pooled data by use of a random-effects model.
  
  
  RESULTS
  Of 2905 identified studies, 15 were eligible and were included in our analysis (N=4348 participants). Compared with other anti-diabetic treatments, GLP-1 agonist and basal insulin combination treatment yielded an improved mean reduction in glycated haemoglobin (HbA1c) of -0·44% (95% CI -0·60 to -0·29), an improved likelihood of achieving the target HbA1c of 7·0% or lower (relative risk [RR] 1·92; 95% CI 1·43 to 2·56), no increased relative risk of hypoglycaemia (0·99; 0·76 to 1·29), and a mean reduction in weight of -3·22 kg (-4·90 to -1·54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA1c of -0·1% (-0·17 to -0·02), with lower relative risk of hypoglycaemia (0·67, 0·56 to 0·80), and reduction in mean weight (-5·66 kg; -9·8 to -1·51).
  
  
  CONCLUSIONS
  GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycaemic control with no increased hypoglycaemia or weight gain. This combination is thus a potential therapeutic strategy that could improve the management of patients with type 2 diabetes.
  
  
  BACKGROUND
  None.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Conrad
authors.initials: C
authors.lastname: Eng
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada. Electronic address: rretnakaran@mtsinai.on.ca.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists*; D015431:Weight Loss
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D018027:Receptors, Glucagon; C517652:hemoglobin A1c protein, human