title: Efficacy and safety of empagliflozin as add-on to metformin for type 2 diabetes: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of ENT, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lai
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Xuping
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Sichuan Medical University, Luzhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan Province, People's Republic of China. hyl3160131@163.com.
authors.forename: Yilan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D008687:Metformin; C570240:empagliflozin
keywords: Empagliflozin; Meta-analysis; Metformin; Systematic review; Type 2 diabetes
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