No. of patients |
16,492 |
5,380 |
14,735 |
Saxagliptin (8,280) |
Alogliptin (2,701) |
Sitagliptin (7,332) |
Placebo (8,212) |
Placebo (2,679) |
Placebo (7,339) |
Study population |
Established CV disease, age ≥40 or Multiple CV risk factors: age ≥55 (male) or ≥60 (female) and at least one of the following: dyslipidemia, hypertension or active smoking |
Acute coronary syndrome within 15-90 days, age ≥18, |
Documented vascular disease in the coronary, cerebral, or peripheral arteries, age ≥50, |
Mean age, yr |
65 |
61 |
66 |
Median duration of diabetes, yr |
10.3 |
7.3 |
10 |
Mean baseline A1c, % (range) |
8.0 (6.5-12.0) |
8.0 (6.5-10.0) |
7.2 (6.5-8.0) |
Hypertension, % |
82 |
83 |
86 |
Dyslipidemia, % |
71 |
Not reported |
77 |
Current smoker, % |
Not reported |
14 |
11 |
Previous heart failure, % |
13 |
28 |
18 |
Median duration of follow-up, yr |
2.1 |
1.5 |
3 |
Comparator |
Standard of care |
Standard of care |
Standard of care |
Aspirin (%) |
Saxagliptin (75.5) |
Alogliptin (90.6) |
Sitagliptin (78.6) |
Placebo (75.0) |
Placebo (90.6) |
Placebo (78.4) |
Statin (%) |
Saxagliptin (78.3) |
Alogliptin (90.6) |
Sitagliptin (79.8) |
Placebo (78.4) |
Placebo (90.3) |
Placebo (80.0) |
β-Blocker (%) |
Saxagliptin (61.6) |
Alogliptin (81.7) |
Sitagliptin (63.4) |
Placebo (61.6) |
Placebo (82.2) |
Placebo (63.7) |
RAAS blockade (%) |
Saxagliptin (81.8) |
Alogliptin (81.5) |
Sitagliptin (78.3) |
Placebo (82.5) |
Placebo (82.5) |
Placebo (79.2) |
Primary end point |
Composite of CV death, myocardial infarction, or ischemic stroke : HR, 1.00 (95% CI, 0.89-1.12) |
Composite of death from CV causes, nonfatal MI, or nonfatal stroke : HR, 0.96 (upper bound of 95% CI, 1.16) |
CV-related death, nonfatal MI, nonfatal stroke, unstable angina requiring hospitalization : HR, 0.98 (ITT P 95% CI, 0.89-1.08) |
Secondary end point |
Composite of death from cardiovascular causes, myocardial infarction, ischemic stroke, hospitalization for unstable angina, coronary revascularization, or heart failure : HR, 1.02 (95% CI, 0.94-1.11) |
Primary endpoint and urgent revascularization due to unstable angina within 24 hours after hospital admission. : HR, 0.95 (upper boundary of the one-sided repeated CI, 1.14) |
Composite end point of: time to first adjudicated confirmed CV-related death, nonfatal MI, nonfatal stroke; time to the occurrence of the individual components of the primary end point; time to all-causes morality; time to hospital admission for adjudicated congestive heart failure : HR, 0.99 (95% CI, 0.89-1.10) |
Hospitalization for heart failure (HHF) |
Rate of HHF: 289 (3.5%) in saxagliptin group vs. 228 (2.8%) in placebo group HR, 1.27 (95% CI, 1.07-1.51; P=0.007) Highest in the first 6 months (HR, 1.80), declining to HR 1.48 after 1 year and 1.28 after 2 years |
Rate of HHF: 106 (3.9%) in alogliptin group vs. 89 (3.3%) in placebo group HR, 1.19 (95% CI, 0.90-1.58; P=0.220) |
Rate of HHF: 228 (3.1%) in sitagliptin group vs. 229 (3.1%) in placebo group HR, 1.00 (95% CI, 0.83-1.20; P=0.98) |
HbA1c at follow-up |
7.7% (saxagliptin) vs. 7.9% (placebo) (P<0.001) |
LSΔ= -0.36% (-0.43 to -0.28; P<0.001) |
LSΔ= -0.29% (-0.32 to -0.27) |
Acute pancreatitis |
Saxagliptin 17 (0.2%) |
Alogliptin 12 (0.4%) |
Sitagliptin 23 (0.3%) |
|
Placebo 9 (0.1%) |
Placebo 8 (0.3%) |
Placebo 12 (0.2%) |