Skip to main content

Table 1 Characteristics of CVOTs

From: Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

  SAVOR TECOS EXAMINE ORIGIN ELIXA LEADER EMPA-REG
Trial characteristic
 Drug Saxagliptin Sitagliptin Alogliptin Glargine Lixisenatide Liraglutide Empagliflozin
 Comparator Placebo Placebo Placebo Placebo Placebo Placebo Placebo
 No. patients 16492 14671 5380 12537 6068 9340 7020
 Duration, years 2.1 3.0 1.5 6.2 2.1 3.8 3.1
 Primary endpoint 3-point MACE 4-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE
 Major secondary endpoint 3-point MACE + hospitalization for unstable angina, coronary revasc.
or HHF
3-point MACE 3-point MACE + urgent revasc. for unstable angina 3-point MACE + revasc. or HHF (co-primary) 3-point MACE + HHF or revasc. 3-point MACE + coronary revasc.
or hospitalization for unstable
angina or HHF
4-point MACE
Pts characteristics
 Age, years (mean ± SD) 65.0 ± 8.5 65.5 ± 8.0 61.0 (median) 63.6 ± 7.8 60.3 ± 9.6 64.3 ± 7.2 63.1 ± 8.7
 Diabetes duration, years 10.3 (IQR 5.2–16.7) 11.6 ± 8.1 7.2 (IQR 2.7–13.7) 5.4 ± 6.0 9.3 ± 8.2 12.8 ± 8.1 57.4 % > 10 years
 Baseline HbA1c 8.0 ± 1.4 7.2 ± 0.5 8.0 ± 1.1 6.4 (IQR 5.8–7.2) 7.6 ± 1.3 8.7 ± 1.5 8.1 ± 0.8
 Baseline BMI 31.1 ± 5.6 30.2 ± 5.6 28.7 (IQR 5.6–68.3) 29.8 ± 5.2 30.2 ± 5.7 32.5 ± 6.3 30.7 ± 5.3
 Insulin users,  % 41.4 23.2 29.9 0 39.1 44.5 48.3
 % with CVD 78.5 74.0 100 58.9 100 81.3 75.6 (CAD)
 % with eGFR <60 ml/min/1.73 m2 15.6 9.4 % (<50 ml/min/1.73 m2) 29.1 N/A 23.2 23.1 26.0
 Annual event rate in placebo arm,  % 3.5 3.8 7.9 2.9 6.3 3.9 4.4
CV outcome
 HR primary endpoint (95 % C.I.) 1.00 (0.89–1.12) 0.98 (0.88–1.09) 0.96 (≤1.16) 1.02 (0.94–1.11) 1.02 (0.89–1.17) 0.87 (0.78–0.97)* 0.86 (0.74–0.99)*
 HR secondary endpoint (95 % C.I.) 1.02 (0.94–1.11) 0.99 (0.89–1.11) 0.95 (≤1.14) 1.04 (0.97–1.11) 0.97 (0.85–1.10) 0.88 (0.81–0.96) 0.89 (0.78–1.01)
 HR HHF (95 % C.I.) 1.27 (1.07–1.51)* 1.00 (0.83–1.20) 1.07 (0.79–1.46) 0.90 (0.77–1.05) 0.96 (0.75–1.23) 0.87 (0.73–1.05) 0.65 (0.50–0.85)*
 HR CV death (95 % C.I.) 1.03 (0.87–1.22) 1.08a 0.79 (0.60–1.04) 1.00 (0.89–1.13) 0.93a 0.68 (0.66–0.93) 0.62 (0.49–0.77)*
 HR any death (95 % C.I.) 1.11 (0.96–1.27) 1.03a 0.88 (0.71–1.09) 0.98 (0.90–1.08) 0.94 (0.78–1.13) 0.85 (0.74–0.97) 0.68 (0.57–0.82)*
 NNT primary endpoint (3 years) N/A N/A N/A N/A N/A 66 61
 NNT death (3 years) N/A N/A N/A N/A N/A 98 39
Efficacy
 HbA1c change,  % −0.3* −0.3* −0.36* −0.3* −0.4* −0.4* −0.3*
 Body weight change, kg −0.4 N/A Neutral +1.1* −0.6* −2.3* −1.4*
 Renal endpoints Albuminuria improved No effect No effect No effect Lower increase in albuminuria Lower rate of
nephropathy events
Lower progression of CKD
  1. Though the ORIGIN trial is not strictly a CVOTs it has been included as being one of the milestone mega-trial in this field
  2. MACE major adverse cardiovascular events, HHF hospitalization for heart failure, Revasc. revascularization, IQR interquartile range, NNT number needed to treat. N/A, not available
  3. * p < 0.05
  4. aExtrapolated from crude data