Is metformin still the most efficacious first-line oral hypoglycaemic drug in treating type 2 diabetes? A network meta-analysis of randomized controlled trials

Obes Rev. 2019 Jan;20(1):1-12. doi: 10.1111/obr.12753. Epub 2018 Sep 17.


Objectives: The objective of the study is to compare the efficacy of hypoglycaemic drugs for type 2 diabetes mellitus (T2DM) by network meta-analysis of randomized controlled trials (RCTs).

Methods: We compared 11 major oral hypoglycaemic drugs under five categories evaluated by RCTs as drug monotherapy for the patients with T2DM, measuring glycosylated haemoglobin (%) or fasting plasma glucose (mmol L-1 ) as outcomes. RCT quality was assessed with the Cochrane risk of bias tool. Network meta-analysis estimated the mean differences and 95% credible intervals. Subgroup and sensitivity analyses were performed to determine the results robustness. The Grading of Recommendation, Assessment, Development, and Evaluation evidence strength was assessed.

Results: Seventy-five RCTs including 33,830 patients were identified. Their study quality was high. Regarding glycosylated haemoglobin, top three anti-diabetics were repaglinide (mean differences -1.39 [95% credible intervals -1.75 to -1.03]), gliclazide (-1.37 [-2.04 to -0.71]) and metformin (-1.13 [-1.37 to -0.90]), against placebo. Regarding fasting plasma glucose, top three anti-diabetics were repaglinide (-2.01 [-2.75 to -0.97]), metformin (-1.72 [-2.16 to -1.27]) and glipizide (-1.57 [-2.44 to -0.64]), against placebo. There was no difference between metformin and repaglinide. Subgroup and sensitivity analyses found the results to be robust. The evidence strength was moderate to high.

Conclusion: This meta-analysis showed that repaglinide and metformin would be the most efficacious oral drugs for first-line monotherapy of T2DM.

Keywords: hypoglycaemic control; network meta-analysis; randomized controlled trials; type 2 diabetes.

Publication types

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

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / therapeutic use*
  • Network Meta-Analysis
  • Treatment Outcome


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