Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis

Diabetes Obes Metab. 2014 May;16(5):433-42. doi: 10.1111/dom.12239. Epub 2013 Dec 16.


Aims: Indirect evidence from randomized controlled trials (RCTs) was used to estimate the effect of dapagliflozin, a new agent with a novel mechanism of action (SGLT-2 inhibition), relative to other anti-diabetes therapies after 1 year of treatment.

Methods: A systematic literature review and Bayesian network meta-analysis (NMA) of RCTs involving anti-diabetes treatments added to metformin were conducted. RCTs enrolling subjects with type 2 diabetes inadequately controlled on metformin monotherapy were included. Comparators included dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), sulphonylureas, glucagon-like peptide-1 (GLP-1) analogues and dapagliflozin. Outcomes of interest were mean change from baseline HbA1c, weight and systolic blood pressure, and incidence of hypoglycaemia.

Results: From 4270 abstracts, six RCTs were included in the primary analysis; no RCTs involving GLP-1 analogues met primary inclusion criteria. All RCTs were actively controlled with sulphonylureas. The mean change in HbA1c from baseline was similar across comparators. The treatment effect (95% credible interval) of dapagliflozin on HbA1c was -0.08% (-0.25, 0.10) relative to DPP-4 inhibitors, -0.02% (-0.24, 0.21) relative to TZDs and 0.00% (-0.16, 0.16) relative to sulphonylureas. Non-sulphonylureas showed significantly lower risk of hypoglycaemia relative to sulphonylureas. Dapagliflozin had a significant effect on weight change: the relative difference was -2.74 kg (-5.35, -0.10) compared with DPP-4 inhibitors, and -4.67 kg (-7.03, -2.35) compared with sulphonylureas. Systolic blood pressure was not meta-analysed due to infrequent reporting.

Conclusion: Compared with DPP-4 inhibitors, TZDs and sulphonylureas, dapagliflozin offers similar HbA1c control after 1 year, with similar or reduced risk of hypoglycaemia and the additional benefit of weight loss, when added to metformin.

Keywords: SGLT2 inhibitor; meta-analysis; metformin; type 2 diabetes.

Publication types

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

MeSH terms

  • Administration, Oral
  • Benzhydryl Compounds / administration & dosage*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Drug Therapy, Combination
  • Female
  • Glucosides / administration & dosage*
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Sulfonylurea Compounds / administration & dosage*
  • Thiazolidinediones / administration & dosage
  • Treatment Outcome


  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Metformin