Introduction
Methods
Search Strategy
Inclusion and Exclusion Criteria
Endpoints and Follow-Up Periods
-
drug-related adverse effects
-
adverse events leading to drug discontinuation
-
serious adverse events (any severe adverse event requiring assistance)
-
death (due to ADEs)
-
hypoglycemia (blood glucose level of ≤ 70 mg/dL or ≤ 3.9 mmol/L)
-
urinary tract infections (UTIs): which were defined as infections of the urinary passage (upper and lower urinary tracts)
-
genital infections: which were defined as infections of the genitalia especially on the external part
Trials (first author) | Outcomes | Follow-up periods |
---|---|---|
Araki et al. [7] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 52 weeks |
Ferrannini et al. [8] | Drug-related adverse effects, serious adverse events, adverse events leading to drug discontinuation, hypoglycemia, UTIs, genital infections | 78 weeks |
Haring et al. [9] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 24 weeks |
Kadowaki et al. [10] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 52 weeks |
Roden et al. [11] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 24 weeks |
Softeland et al. [12] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 24 weeks |
Takkanen et al. [13] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 12 weeks |
Zinman et al. [14] | Drug-related adverse effects, adverse events leading to drug discontinuation, serious adverse events, death, hypoglycemia, UTIs, genital infections | 3.1 years |
Data Extraction and Quality Assessment
-
type of study (priority was given to randomized controlled trials)
-
names of first author
-
year of publication
-
time of patients’ enrollment
-
total number of patients who were treated with 10 and 25 mg empagliflozin, respectively
-
other anti-diabetic medications which were used
-
duration of T2DM
-
length of follow-up periods
-
reported ADEs
-
total number of male and female patients with UTIs
-
range of glycated hemoglobin (HbA1c) in patients
-
baseline features of participants in the trials
-
methodological qualities of the trials.
Statistical Analysis
Compliance with Ethics Guidelines
Results
Searched Outcomes
General Features of the Trials
Trials | No of patients treated with 10 mg empagliflozin (n) | No of patients treated with 25 mg empagliflozin (n) | Enrollment period | Type of study | Bias risk gradea |
---|---|---|---|---|---|
Araki et al. [7] | 548 | 549 | 2011–2013 | RCT | B |
Ferrannini et al. [8] | 272 | 275 | 2009–2011 | RCT | B |
Haring et al. [9] | 217 | 213 | 2010–2012 | RCT | B |
Kadowaki et al. [10] | 267 | 265 | 2010–2014 | RCT | B |
Roden et al. [11] | 224 | 223 | 2010–2012 | RCT | A |
Softeland et al. [12] | 112 | 110 | 2013–2015 | RCT | B |
Takkanen et al. [13] | 276 | 276 | 2011–2012 | RCT | B |
Zinman et al. [14] | 2345 | 2342 | 2010–2013 | RCT | A |
Total no of patients (n) | 4261 | 4253 |
Baseline Features of the Participants
Trials | Age (years) | Males (%) | HbA1c (%) | BMI (kg/m2) |
---|---|---|---|---|
10 mg/25 mg | 10 mg/25 mg | 10 mg/25 mg | 10 mg/25 mg | |
Araki et al. [7] | 60.8/59.6 | 58.5/72.3 | 7.99/8.06 | 24.6/25.2 |
Ferrannini et al. [8] | 59.5/59.5 | 48.1/52.7 | 7.89/8.00 | 28.9/28.1 |
Haring et al. [9] | 55.5/55.6 | 58.0/56.0 | 7.94/7.86 | 29.1/29.7 |
Kadowak et al. [10] | 57.3/57.9 | 75.7/74.0 | 7.94/7.93 | 25.4/25.4 |
Roden et al. [11] | 56.2/53.8 | 63.0/65.0 | 7.87/7.86 | 28.3/28.2 |
Softeland et al. [12] | 54.3/55.4 | 60.6/64.5 | 7.97/7.97 | 31.2/29.9 |
Takkanen et al. [13] | 60.6/59.9 | 62.0/56.5 | 7.87/7.92 | 32.4/33.0 |
Zinman et al. [14] | 61.1/61.1 | 73.1/73.9 | 8.06/8.05 | 26.8/26.5 |
Trials | Other anti-diabetic agents which were used | Duration of T2DM (years) |
---|---|---|
Araki et al. [7] | Empagliflozin + sulphonyl urea or metformin or thiazolidinedione or alpha-glucosidase inhibitor or glinide or dipeptidyl-peptidase-4 | 1 to ≥ 10 |
Ferrannini et al. [8] | Empagliflozin mono-therapy and empagliflozin + metformin | 1 to ≥ 5 |
Haring et al. [9] | Empagliflozin + metformin | 1 to ≥ 10 |
Kadowaki et al. [10] | Empagliflozin monotherapy | – |
Roden et al. [11] | Empagliflozin monotherapy | 1 to ≥ 10 |
Softeland et al. [12] | Empagliflozin + linagliptin 5 mg and metformin | 1 to ≥ 10 |
Takkanen et al. [13] | Empagliflozin monotherapy | 1 to ≥ 10 |
Zinman et al. [14] | Empagliflozin + metformin and other anti-diabetic drugs (unspecified) | – |