European Journal of Clinical Pharmacology

, Volume 72, Issue 6, pp 655–663 | Cite as

Efficacy and safety of empagliflozin as add-on to metformin for type 2 diabetes: a systematic review and meta-analysis

  • Xiaoyan Zhong
  • Dan Lai
  • Yun Ye
  • Xuping Yang
  • Bin Yu
  • Yilan Huang



To assess the efficacy and safety of empagliflozin (EMPA) as add-on to metformin (MET) in patients with type 2 diabetes mellitus (T2DM).


We searched PubMed, Embase, Medline, OVID, Cochrane Library and Web of Science. Randomized controlled trials of EMPA as add-on to MET for T2DM were included. Two investigators independently selected studies, extracted data and assessed the risk of bias. A meta-analysis was conducted by using RevMan 5.3 software and Stata 12 software.


Seven trials including 4256 patients were analysed. Compared with placebo, two different doses of EMPA significantly reduced glycated haemoglobin (HbA1c) [10 mg: weighted mean difference (WMD) −0.57 %; 95 % confidence interval (CI) −0.65 to −0.49 %, P < 0.00001; 25 mg: WMD −0.65 %; 95 % CI −0.72 to −0.57 %, P < 0.00001]. Compared with active comparators (two sitagliptin, one linagliptin and one glimepiride), 10 mg of EMPA provided a similar reduction in HbA1c [WMD −0.10 %; 95 % CI −0.23 to 0.03 %, P = 0.13], while 25 mg of EMPA provided a significantly greater reduction in HbA1c [WMD −0.13 %; 95 % CI −0.20 to −0.06 %, P = 0.0005]. In addition, EMPA as add-on to MET also had a favourable effect on body weight and blood pressure. The risk of hypoglycaemia in the EMPA group was similar to the placebo group or active comparator group.


EMPA as add-on to MET was well tolerated and provided additional benefits beyond glucose lowering, such as weight loss and blood pressure reduction. However, high-quality trials with large samples are still needed in order to confirm their long-term safety.


Empagliflozin Metformin Type 2 diabetes Systematic review Meta-analysis 

Supplementary material

228_2016_2010_MOESM1_ESM.doc (94 kb)
ESM 1 (DOC 94 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Xiaoyan Zhong
    • 1
  • Dan Lai
    • 2
  • Yun Ye
    • 1
  • Xuping Yang
    • 1
  • Bin Yu
    • 3
  • Yilan Huang
    • 1
  1. 1.Department of PharmacyThe Affiliated Hospital of Luzhou Medical CollegeLuzhouPeople’s Republic of China
  2. 2.Department of ENTThe Affiliated Hospital of Luzhou Medical CollegeLuzhouPeople’s Republic of China
  3. 3.College of PharmacySichuan Medical UniversityLuzhouPeople’s Republic of China

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