QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(三十一)
, active-controlled, parallel group study(NCT02681094) in T2DM patients with an HbA1c ≥7.5% and ≤10.0%. Patients were on a stable dose ofmetformin HCl (≥1500 mg per day) for at least 8 weeks prior to being randomized to one of three doubleblindtreatment groups to receive 5 mg dapagliflozin and 5 mg saxagliptin added to metformin, 5 mgsaxagliptin and placebo added to metformin, or 5 mg dapagliflozin and placebo added to metformin.
At Week 24, concomitant addition of 5 mg dapagliflozin and 5 mg saxagliptin plus metformin resulted instatistically significant decreases in HbA1c, and a larger proportion of patients achieving the therapeutic glycemic goal of HbA1c <7%, compared to dapagliflozin plus metformin or saxagliptin plus metformin
(see Table 11).
Table 11: HbA1c Results at Week 24 with the Combination of 5 mg Dapagliflozin and
5 mg Saxagliptin plus Metformin*
Efficacy Parameter
5 mg Dapagliflozin and 5 mg Saxagliptin + Metformin
5 mg Dapagliflozin and
5 mg Saxagliptin
+
Metformin
5 mg Dapagliflozin
+
Metformin
5 mg Saxagliptin
+
Metformin
N† 290 289 291
Baseline (mean) 8.1 8.2 8.3
Change from
baseline (adjusted
mean) (95% CI)
−1.02
(−1.13, −0.90)
−0.62
(−0.73, −0.51)
−0.69
(−0.80, −0.59)
Difference from
dapagliflozin +
metformin (adjusted
mean) (95% CI)
−0.40‡
(−0.55, −0.24)
Difference from
saxagliptin +
metformin (adjusted
mean)
(95% CI)
−0.32‡
(−0.48, −0.17)
Percent of patients
achieving HbA1c
<7%
42.8 21.8§ 28.5¶
* Analysis of Covariance including all post-baseline data regardless of rescue or treatment discontinuation. Modelestimates calculated using multiple imputation to model washout of the treatment effect using control arm datafor all subjects having missing Week 24 data. † The number of randomized subjects who took at least one dose of double-blind study medication and had abaseline value for HbA1c.
‡ p-value <0.0001.
§ p-value <0.0001 vs. dapagliflozin and saxagliptin plus metformin.
¶ p-value = 0.0018 vs. dapagliflozin and saxagliptin plus metformin.
The adjusted mean change from baseline for body weight at Week 24, using values regardless of rescue ortreatment discontinuation, was -2.0 kg for the 5 mg dapagliflozin and 5 mg saxagliptin plus metformingroup, -2.1 kg for the 5 mg dapagliflozin plus metformin group, and -0.4 kg for the 5 mg saxagliptin plus
metformin group. The difference in mean body weight between the 5 mg dapagliflozin and 5 mgsaxagliptin plus metformin group and the 5 mg dapagliflozin plus metformin group was -1.6 kg (95%CI [-2.1, -1.0]).
The second study was a 24-week randomized, double-blind, active comparator-controlled superioritystudy (NCT016060007) that compared once daily 10 mg dapagliflozin and 5 mg saxagliptincoadministered in combination with metformin XR with either 10 mg dapagliflozin and placebo added to metformin or 5 mg saxagliptin and placebo added to metformin in T2DM adult patients with inadequateglycemic control on metformin alone (HbA1c ≥8% and ≤12%).
At Week 24, concomitant addition of 10 mg dapagliflozin and 5 mg saxagliptin plus metformin resultedin statistically significant decreases in HbA1c, and a larger propo |
