Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis

Diabetes Obes Metab. 2012 Sep;14(9):810-20. doi: 10.1111/j.1463-1326.2012.01606.x. Epub 2012 Apr 29.


Aim: Most guidelines recommend metformin as first-line therapy in patients with type 2 diabetes. However, the choice of a second-line drug lacks consistent consensus. We aimed to assess available information of antidiabetic drugs added to metformin on the change in glycated haemoglobin A1c (A1C), risk of hypoglycaemia and change in body weight.

Methods: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) written in English through December 2011. We analysed direct and indirect comparisons of different treatments using Bayesian network meta-analysis.

Results: Thirty-nine RCTs involving 17 860 individuals were included. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in A1C compared with sulfonylureas, glinides, thiazolidinediones, α-glucosidase inhibitors and DPP-4 inhibitors [-0.20% (95% CI -0.34 to -0.04%), -0.31% (95% CI -0.61 to -0.02%), -0.20% (95% CI -0.38 to -0.00), -0.36% (95% CI -0.64 to -0.07%), -0.32% (95% CI -0.47 to -0.17%), respectively] and was comparable with basal insulin and biphasic insulin. A1C decrease was greater for sulfonylureas compared with DPP-4 inhibitors [-0.12% (-0.23 to -0.03%)], and for biphasic insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin, and weight loss was seen with α-glucosidase inhibitors and GLP-1 analogues.

Conclusions: Biphasic insulin, GLP-1 analogues and basal insulin were ranked the top three drugs in terms of A1C reduction. GLP-1 analogues did not increase the risk of hypoglycaemia and resulted in a significant decrease in body weight. Most oral antidiabetic drugs had similar effects on A1C, but some agents had a lower risk of hypoglycaemia and body weight gain.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / therapeutic use*
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Metformin