Effects of three injectable antidiabetic agents on glycaemic control, weight change and drop-out in type 2 diabetes suboptimally controlled with metformin and/or a sulfonylurea: A network meta-analysis

Diabetes Res Clin Pract. 2015 Sep;109(3):451-60. doi: 10.1016/j.diabres.2015.05.048. Epub 2015 Jun 5.


Aims: The objective of this review was to assess glucagon-like peptide-1 receptor agonists (GLP-1 RAs), basal insulin, and premixed insulin among participants with type 2 diabetes inadequately controlled with metformin and/or a sulfonylurea.

Methods: We searched PubMed, EmBase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs) for a network meta-analysis.

Results: A total of 17 RCTs involving 5874 adult individuals were included. Compared with placebo, all three therapies showed a significant effect on achieving target glycated hemoglobin (HbA1c) (GLP-1 RAs: 31.7%, 95% CI, 24.7-38.6%; premixed insulin: 31.1%, 95% CI, 20.4-41.8%; basal insulin: 26.0%, 95% CI, 16.4-35.7%). However, there was no significant difference between the three therapies. A similar result was found in HbA1c reduction. The use of GLP-1 RAs resulted in significant body weight loss (-3.73 kg, 95% CI, -4.52 to -2.95 kg vs. basal insulin and -5.27 kg, 95% CI, -6.17 to -4.36 kg vs. premixed insulin) but there was a higher drop-out rate of participants. Premixed insulin seemed associated with more severe hypoglycemic episodes.

Conclusions: The three injectables had similar impact on glycemic control but other differentiating features relevant to the management of type 2 diabetes with GLP-1 RAs having the most favorable profile.

Keywords: Glucagons-like peptide-1 receptor agonist; Injectable antidiabetic agent; Metformin; Network meta-analysis; Sulfonylurea; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Community Networks / statistics & numerical data
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glucagon-Like Peptide 1 / agonists
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Injections
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Male
  • Metformin / therapeutic use*
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Failure


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Glucagon-Like Peptide 1
  • Metformin