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

• Published in: European journal of clinical pharmacology Vol. 72; no. 6; pp. 655 - 663
• Main Authors: Zhong, Xiaoyan, Lai, Dan, Ye, Yun, Yang, Xuping, Yu, Bin, Huang, Yilan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2016; Springer Nature B.V
• Subjects: Benzhydryl Compounds - therapeutic use; Biomedical and Life Sciences; Biomedicine; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Drug Therapy, Combination; Glucosides - therapeutic use; Humans; Hypoglycemic Agents - therapeutic use; Meta-analysis; Metformin - therapeutic use; Pharmacology; Pharmacology/Toxicology; Randomized Controlled Trials as Topic; Review; Safety; Treatment Outcome; Type 2 diabetes; Empagliflozin; Systematic review; Metformin; Meta-analysis
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-016-2010-8

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