Table 1 Characteristics of CVOTs

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)

1.08^a

0.79 (0.60–1.04)

1.00 (0.89–1.13)

0.93^a

0.68 (0.66–0.93)

0.62 (0.49–0.77)*

 HR any death (95 % C.I.)

1.11 (0.96–1.27)

1.03^a

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