QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(三十三)
in
HbA1c (%) at week 24‡
Baseline (mean) 8.0 7.9
Change from baseline (adjusted mean§
)
95% Confidence Interval
−0.5
(−0.6, −0.4)
−0.2
(−0.3, −0.1)
Difference from placebo (adjusted mean)
95% Confidence Interval
−0.4¶
(−0.5, −0.2)
Percent of patients achieving HbA1c <7% 35.3 23.1
*There were 6.5% (n=10) of randomized subjects in the saxagliptin arm and 3.1% (n=5) in the placebo arm forwhom change from baseline HbA1c data was missing at Week 24. Of the subjects who discontinued studymedication early, 9.1% (1 of 11) in the saxagliptin arm and 16.7% (1 of 6) in the placebo arm had HbA1cmeasured at Week 24.
†N is the number of randomized and treated patients.
‡ Analysis of Covariance including all post-baseline data regardless of rescue or treatment discontinuation.
Model estimates calculated using multiple imputation to model washout of the treatment effect using placebodata for all subjects having missing Week 24 data.
§Least squares mean adjusted for baseline value.
¶ p-value <0.0001.
14.3 Cardiovascular Safety Trial
The cardiovascular risk of saxagliptin was eva luated in SAVOR (Saxagliptin Assessment of VascularOutcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction), amulticenter, multinational, randomized, double-blind trial comparing saxagliptin (N=8280) to placebo (N=8212), in adult patients with type 2 diabetes at high risk for atherosclerotic cardiovascular disease. Ofthe randomized study subjects, 97.5% completed the trial, and the median duration of follow-up was
approximately 2 years (NCT01107886).
Subjects were at least 40 years of age, had HbA1c ≥6.5%, and multiple risk factors (21% of randomizedsubjects) for cardiovascular disease (age ≥55 years for men and ≥60 years for women plus at least oneadditional risk factor of dyslipidemia, hypertension, or current cigarette smoking) or established (79% ofthe randomized subjects) cardiovascular disease defined as a history of ischemic heart disease, peripheralvascular disease, or ischemic stroke. Overall, the use of diabetes medications was balanced acrosstreatment groups (metformin 69%, insulin 41%, sulfonylureas 40%, and TZDs 6%). The use ofcardiovascular disease medications was also balanced (angiotensin-converting enzyme [ACE] inhibitorsor angiotensin receptor blockers [ARBs] 79%, statins 78%, aspirin 75%, beta-blockers 62%, and
non-aspirin antiplatelet medications 24%).
The majority of subjects were male (67%) and Caucasian (75%) with a mean age of 65 years.
Approximately 16% of the population had moderate (eGFR ≥30 to ≤50 mL/min/1.73 m2) to severe(eGFR <30 mL/min/1.73 m2) renal impairment, and 13% had a prior history of heart failure.
QTERNMET XR is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2. Subjects hada median duration of type 2 diabetes mellitus of approximately 10 years and a mean baseline HbA1c levelof 8.0%.
The primary analysis in SAVOR was time to first occurrence of a Major Adverse Cardiac Event (MACE).
A major adverse cardiac event in SAVOR was defined as a cardiovascular death or a nonfatal myocardialinfarction (MI) or a nonfatal ischemic stroke. The incidence rate of MACE was similar in both treatmentarms: 3.8 MACE per 100 patient-years on placebo vs. 3.8 MACE per 100 patient-years o |
