SYNJARDYXR(empagliflozin and metformin hydrochloride extended-release) tablets(二十八)
for empagliflozin 25 mg, n=215, for placebo, n=224
Empagliflozin
10 mg + Metformin
+ SU
N=225 Empagliflozin
25 mg + Metformin
+ SU
N=216 Placebo +
Metformin + SU
N=225
HbA1c (%)a
Baseline (mean) 8.1 8.1 8.2
Change from baseline (adjusted mean) -0.8 -0.8 -0.2
Difference from placebo (adjusted mean) (95% CI) -0.6b (-0.8, -0.5) -0.6b (-0.7, -0.4) --
Patients [n (%)] achieving HbA1c <7% 55 (26%) 65 (32%) 20 (9%)
FPG (mg/dL)c
Baseline (mean) 151 156 152
Change from baseline (adjusted mean) -23 -23 6
Difference from placebo (adjusted mean) -29 -29 --
Body Weight
Baseline mean in kg 77 78 76
% change from baseline (adjusted mean) -2.9 -3.2 -0.5
Difference from placebo (adjusted mean) (95% CI) -2.4b (-3.0, -1.8) -2.7b (-3.3, -2.1) --
Active-Controlled Study vs Glimepiride in Combination with Metformin
The efficacy of empagliflozin was eva luated in a double-blind, glimepiride-controlled, study in 1545 patients with type 2 diabetes with insufficient glycemic control despite metformin therapy.
Patients with inadequate glycemic control and an HbA1c between 7% and 10% after a 2-week run-in period were randomized to glimepiride or empagliflozin 25 mg.
At Week 52, empagliflozin 25 mg and glimepiride lowered HbA1c and FPG (see Table 10, Figure 3). The difference in observed effect size between empagliflozin 25 mg and glimepiride excluded the pre-specified non-inferiority margin of 0.3%. The mean daily dose of glimepiride was 2.7 mg and the maximal approved dose in the United States is 8 mg per day.
Table 10 Results at Week 52 from an Active-Controlled Study Comparing Empagliflozin to Glimepiride as Add-On Therapy in Patients Inadequately Controlled on Metformin
aModified intent to treat population. Last observation on study (LOCF) was used to impute data missing at Week 52. At Week 52, data was imputed for 15.3% and 21.9% of patients randomized to empagliflozin 25 mg and glimepiride, respectively.
bNon-inferior, ANCOVA model p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and region)
cANCOVA p-value <0.0001 (Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.)
dFPG (mg/dL); for empagliflozin 25 mg, n=764, for placebo, n=779
Empagliflozin 25 mg +
Metformin
N=765 Glimepiride +
Metformin
N=780
HbA1c (%)a
Baseline (mean) 7.9 7.9
Change from baseline (adjusted mean) -0.7 -0.7
Difference from glimepiride (adjusted mean) (97.5% CI) -0.07b (-0.15, 0.01) --
FPG (mg/dL)d
Baseline (mean) 150 150
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