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Copyright ©2014 Baishideng Publishing Group Inc.
World J Diabetes. Jun 15, 2014; 5(3): 399-406
Published online Jun 15, 2014. doi: 10.4239/wjd.v5.i3.399
Table 1 Summary of clinical trials of canagliflozin
References/trial name (n = sample size)Study population and duration of the studyStudy drugsChange in HbA1c from the baseline (in percent)Change in FBG from baselineChange in body weight from baselineOther parameters (least square mean change)
Stenlöf et al[19] (n = 584)T2DM patients on diet and exercise with inadequate glycemic control Duration of the study = 26 wkCFZ = 100 mg/300 mg OD vs PL-0.77% to -1.03% (CFZ 100 mg/300 mg, P < 0.001 vs PL)-27 mg/dL to -35 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs PL)% Body weight reduction -2.8% to -3.9% (CFZ 100 mg/300 mg, P < 0.001 vs PL)ΔPPBG = -43 to -59 mg/dL (CFZ 100 mg/300 mg) ΔSBP = -3.3 to -5.0 mmHg (CFZ 100 mg/300 mg, P < 0.001 vs PL) ΔDBP = -1.7 to -2.1 mmHg (CFZ 100 mg/300 mg vs PL) ΔHDL = CFZ 100 mg = 11.2% (P < 0.001 vs PL) CFZ 300 mg = 10.6% (P < 0.01 vs PL) ΔLDL = 2.9% to 7.1% (CFZ 100 mg/300 mg vs PL) ΔTG = 2.5% to -2.3% (CFZ 100 mg/300 mg vs PL) HOMA-%B = 9.9% to 20.3% (CFZ 100 mg/300 mg vs PL)
CANTATA-D[20]26-wk extension studyAt the end of 26 wkAt the end of 26 wkAt the end of 26 wkAt the end of 26 wk
(n = 1284)T2DM patients with inadequate glycemic control on protocol specified MET-IR monotherapy with HbA1c: 7.0% to 10.5%, FBG < 270 mg/dLCFZ = 100 mg/300 mg OD + MET-IR vs PL + MET-IR for first 26 wk-0.79% to -0.94% (CFZ 100 mg/300 mg, P < 0.001 vs PL)-27.3 mg/dL to -37.8 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs PL)% Body weight reduction -3.7% to -4.2% (CFZ 100 mg/300 mg, P < 0.001 vs PL)ΔPPBG = -47.9 mg/dL to -57.1 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs PL) SITA = -49.3 mg/dL ΔSBP = -3.84 mmHg to -5.06 mmHg (CFZ 100 mg/300 mg, P < 0.001 vs PL), SITA = -1.83 mmHg ΔTG = CFZ 100 mg = 1.6%, P = 0.7 vs PL, CFZ 300 mg = -1.4%, P = 0.2 vs PL, SITA = 1.0% ΔHDL = 10.4% to 12.1% (CFZ 100 mg/300 mg, P < 0.001 vs PL), SITA = 5%
CFZ = 100 mg/300 mg OD + MET-IR vs SITA 100 mg + MET-IR for next 26 wkSITA = -0.82%SITA = -20.2 mg/dLSITA = -1.2%
At the end of 52 wkAt the end of 52 wkAt the end of 52 wkAt the end of 52 wk
-0.73% to -0.88% (CFZ 100 mg/300 mg)-26.2 mg/dL to -35.2 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs SITA)-3.8% to -4.2% (CFZ 100 mg/300 mg, P < 0.001 vs SITA)ΔSBP = -3.53 mmHg to -4.65 mmHg (CFZ 100 mg/300 mg, P < 0.001 vs SITA) SITA = -0.66 mmHg ΔTG = CFZ 100 mg = 1.9%, P = 0.46 vs SITA CFZ 300 mg = 2.7%, P = 0.32 vs SITA SITA = -0.4% ΔHDL = 11.2% to 13.3% (CFZ 100 mg/300 mg, P < 0.001 vs SITA), SITA = 6.0%
SITA = -0.73%SITA = -17.7 mg/dLSITA = -1.3%
Guthrie et al[21]26-wk extension studyAt the end of 26 wkAt the end of 26 wkAt the end of 26 wkAt the end of 26 wk
Forst et al[22] CANTATA-MP (n = 344)T2DM patients currently treated with PPAR gamma agent (PIO or ROSI) and MET with HbA1c: 7%-10.5% and FBG < 270 mg/dLCFZ = 100 mg/300 mg OD + MET + PIO vs PL + MET + PIO for first 26 wk CFZ = 100 mg/300 mg OD + MET + PIO vs SITA 100 mg + MET + PIO for next 26 wk-0.89% to -1.03% (CFZ 100 mg/300 mg, P < 0.001 vs PL)-26.8 mg/dL to -33.2 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs PL)-2.8% to -3.8% (CFZ 100 mg/300 mg, P < 0.001 vs PL)ΔSBP = CFZ 100 mg = -5.30 mmHg (P = 0.005 vs PL) CFZ 300 mg = -4.70 mmHg (P = 0.016 vs PL) ΔTG = CFZ 100 mg = 3.2% (P = 0.034 vs PL) CFZ 300 mg = -1.7% (P = 0.003 vs PL) ΔHDL = CFZ 100 mg = 7.2% (P = 0.01 vs PL) CFZ 300 mg = 8.9% (P < 0.001 vs PL) HOMA-%B = 15.19% to 18.14% (CFZ 100 mg/300 mg, P < 0.01 vs PL)
At the end of 52 wkAt the end of 52 wkAt the end of 52 wkAt the end of 52 wk
-0.92% to -1.03% (CFZ 100 mg/300 mg)-26.7 mg/dL to -31.5 mg/dL (CFZ 100 mg/300 mg)-2.7% to -3.7% (CFZ 100 mg/300 mg)ΔSBP = -3.4 to -3.7 mmHg (CFZ 100 mg/300 mg) ΔDBP = -2.5 to -2.7 mmHg (CFZ 100 mg/300 mg) ΔHDL = CFZ 100 mg = 7.0% CFZ 300 mg = 11.4% ΔLDL = 10.9% to 14.3% (CFZ 100 mg/300 mg) ΔTG = 4.7% to -0.6% (CFZ 100 mg/300 mg)
Cefalu et al[23] CANTATA-SU (n = 1450)T2DM patients with HbA1c: 7%-9.5% on stable MET therapy ≥ 1500 mg/d, BMI = 22-45kg/m2, FBG ≤ 270mg/dL Duration of the study = 52 wkCFZ = 100 mg/300mg OD + MET vs GLIM 6 mg/8 mg OD + MET-0.82% to -0.93% (CFZ 100 mg/300 mg)-1.35 mmol/L to -1.52 mmol/L (CFZ 100 mg/300 mg)-4.2% to -4.7% (CFZ 100 mg/300 mg, P < 0.001 vs GLIM)ΔSBP = -3.3 to -4.6 mmHg (CFZ 100 mg/300 mg) GLIM = 0.2 mmHg ΔDBP = -1.8 to -2.5 mmHg (CFZ 100 mg/300 mg) GLIM = -0.1 mmHg ΔTG = CFZ 100 mg = -3.7% CFZ 300 mg = 2.3% GLIM = 9.5% ΔHDL = CFZ 100 mg = 7.9% CFZ 300 mg = 9.0% GLIM = 0.3% ΔLDL = 9.6% to 14.1% (CFZ 100 mg/300 mg) GLIM = 5%
GLIM = -0.81%GLIM = -1.02 mmol/LGLIM = 1%
Wilding et al[24]26-wk extension studyAt the end of 26 wkAt the end of 26 wkAt the end of 26 wkAt the end of 26 wk
CANTATA-MSU (n = 469)T2DM patients currently treated with MET and SU with HbA1c: 7%-10.5% and FBG < 270 mg/dLCFZ = 100 mg/300 mg OD + MET + SU vs PL + MET + SU-0.85% to -1.06% (CFZ 100 mg/300 mg, P < 0.001 vs PL)-18.2 mg/dL to -30.5 mg/dL (CFZ 100 mg/300 mg, P < 0.001 vs PL)-2.1% to -2.6% (CFZ 100 mg/300 mg, P < 0.001 vs PL)ΔSBP = CFZ 100 mg = -4.89 mmHg (P = 0.07 vs PL) CFZ 300 mg = -4.27 mmHg (P = 0.2 vs PL) ΔTG = CFZ 100 mg = 5.4% (P = 0.256 vs PL) CFZ 300 mg = 8.5% (P = 0.57 vs PL) ΔHDL = CFZ 100 mg = 5.7% (P = 0.153 vs PL) CFZ 300 mg = 6.5% (P = 0.056 vs PL)
Schernthaner et al[25] CANTATA-D2 (n = 755)T2DM patients currently treated with MET and SU with HbA1c: 7%-10.5% and FBG < 300 mg/dL Duration of the study = 52 wkCFZ = 300 mg OD + MET + SU vs SITA = 100 mg OD + MET + SUCFZ 300 mg = -1.03% (P < 0.001 vs SITA) SITA = -0.66%CFZ 300 mg = -29.9 mg/dL (P < 0.001 vs SITA) SITA = -5.85 mg/dLCFZ 300 mg = -2.5% (P < 0.001 vs SITA) SITA = 0.3%ΔSBP = CFZ 300 mg = -5.06 mmHg (P < 0.001 vs SITA) SITA = 0.85 mmHg ΔTG = CFZ 300 mg = 9.6% (P = 0.554 vs SITA) SITA = 11.9% ΔHDL = CFZ 300 mg = 7.6% (P < 0.001 vs SITA) SITA = 0.6%
Devineni et al[26] (n = 29)T2DM patients not optimally controlled on insulin and up to one oral AHA with BMI: 25-45 kg/m2, FBG: 3.3-5.5 mmol/L, HbA1c: 7%-10.5% and serum creatinine: < 132.6 mmol/L for males and < 123.8 mmol/L for women Duration of the study = 28 dCFZ 100 mg OD/300 mg bid + Insulin + upto one AHA vs PL + insulin + upto one AHA-0.73% to -0.92% (CFZ 100 mg/300 mg)-2.11 mmol/L to -2.35 mmol/L (CFZ 100 mg/300 mg)-0.73 kg to -1.19 kg (CFZ 100 mg/300 mg)ΔUGE = 71.9 g/d to 129.2 g/d
Rosenstock et al[27] (n = 451)T2DM patients under stable MET monotherapy (≥ 1500 mg/d) with HbA1c: 7%-10%, BMI: 24-45 kg/m2, serum creatinine: < 1.5mg/dL for males and < 1.4 mg/dL for females Duration of the study = 12 wkCFZ = 50/100/200/300 mg OD or 300 mg bid + MET vs PL + MET vs SITA 100 mg OD + METCFZ 50 mg = -0.79% 100 mg = -0.76% 200 mg = -0.70% 300 mg = -0.92% 300 mg bid = -0.95% SITA = -0.74%CFZ 50 mg = -16.2 mg/dL 100 mg = -25.2 mg/dL 200 mg = -27.0 mg/dL 300 mg = -25.2 mg/dL 300 mg bid = -3.4 mg/dL SITA = -12.6 mg/dLCFZ 50 mg = -2.3% 100 mg = -2.60% 200 mg = -2.70% 300 mg = -3.40% 300 mg bid = -3.4% SITA = -0.60%ΔSBP = -3.3 to -5 mmHg (CFZ 100 mg/300 mg) SITA = -0.8 mmHg ΔDBP = -1.7 to -2.1 mmHg (CFZ 100 mg/300 mg) SITA = -0.6 mmHg ΔTG = CFZ 100 mg = 2.5% CFZ 300 mg = -2.3% ΔHDL = CFZ 100 mg = 11.2% CFZ 300 mg = 10.6% ΔLDL = 2.9% to 7.1% (CFZ 100 mg/300 mg) HOMA-%B = CFZ 50-300 mg OD = 6% to 18% CFZ 300 mg bid = 16% SITA = 10%
ClinicalTrials. gov identifier: NCT01064414[28] (n = 272)26-wk extension studyAt the end of 26 wkAt the end of 26 wk
T2DM patients with or without AHA, on regular diet and exercise with moderate renal impairmentCFZ = 100 mg/300 mg OD with or without AHA vs PL with or without AHA-0.33% to -0.44% (CFZ 100 mg, P = 0.01 vs PL, CFZ 300 mg, P < 0.001 vs PL)CFZ 100 mg = -14.9 mg/dL, P = 0.02 CFZ 300 mg = -11.7 mg/dL, P = 0.06Information was not availableInformation was not available