Supplementary Fig. 1
Cardiovascular risk factors from the three cardiovascular outcome trials: (A) glycosylated hemoglobin, (B) systolic blood pressure, (C) body weight, and (D) heart rate. CI, confidence interval; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6, Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; EXSCEL, Exenatide Study of Cardiovascular Event Lowering Trial; GLP-1, glucagon-like peptide 1.
dmj-43-410-s003.pdf
Fig. 1The composite analysis of the risk of major adverse cardiovascular events (MACEs) from three cardiovascular outcome trials, expressed as relative risk (RR): (A) three-point MACE, (B) cardiovascular death, (C) non-fatal myocardial infarction, and (D) non-fatal stroke. CI, confidence interval; GLP-1, glucagon-like peptide 1; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6, Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; EXSCEL, Exenatide Study of Cardiovascular Event Lowering Trial.
Fig. 2The combined subgroup analysis of the risk of major adverse cardiovascular events from three cardiovascular outcome trials. RR, relative risk; CI, confidence interval; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycosylated hemoglobin; CVD, cardiovascular disease.
Table 1CV outcomes
Variable |
LEADER |
SUSTAIN-6 |
EXSCEL |
Liraglutide |
Placebo |
Semaglutide |
Placebo |
Exenatide QW |
Placebo |
No. of participants |
4,668 |
4,672 |
1,648 |
1,649 |
7,356 |
7,396 |
Follow-up (median) |
3.8 |
3.8 |
2.1 |
2.1 |
3.2 |
3.2 |
Racial composition (incidence proportion for MACE) |
|
|
|
|
|
|
White |
494/3,616 (13.7) |
543/3,622 (15.0) |
93/1,384 (6.7) |
118/1,352 (8.7) |
683/5,554 (12.3) |
712/5,621 (12.7) |
Black |
47/370 (12.7) |
59/407 (14.5) |
5/108 (4.6) |
7/113 (6.2) |
43/442 (9.7) |
62/436 (14.2) |
Asian |
40/471 (8.5) |
56/465 (12.0) |
8/121 (6.6) |
17/152 (11.2) |
60/725 (8.3) |
74/727 (10.2) |
Other |
27/211 (12.8) |
36/178 (20.2) |
2/35 (5.7) |
4/32 (12.5) |
53/633 (8.4) |
56/609 (9.2) |
Primary outcome |
|
|
|
|
|
|
No. of events |
608 (13.0) |
694 (14.9) |
108 (6.6) |
146 (8.9) |
839 (11.4) |
905 (12.2) |
HR (95% CI) |
0.87 (0.78–0.97) |
|
0.74 (0.58–0.95) |
|
0.91 (0.83–1.00) |
|
P value for noninferiority |
<0.001 |
|
<0.001 |
|
<0.001 |
|
P value for superiority |
0.01 |
|
0.02 |
|
0.06 |
|
CV death |
|
|
|
|
|
|
No. of events |
219 (4.7) |
278 (6.0) |
44 (2.7) |
46 (2.8) |
229 (3.1) |
258 (3.5) |
HR (95% CI) |
0.78 (0.66–0.93) |
|
0.98 (0.65–1.48) |
|
0.88 (0.73–1.05) |
|
P value |
0.007 |
|
0.92 |
|
NR |
|
Non-fatal MI |
|
|
|
|
|
|
No. of events |
281 (6.0) |
317 (6.8) |
47 (2.9) |
64 (3.9) |
455 (6.2) |
470 (6.4) |
HR (95% CI) |
0.88 (0.75–1.03) |
|
0.74 (0.51–1.08) |
|
0.95 (0.84–1.09) |
|
P value |
0.11 |
|
0.12 |
|
NR |
|
Non-fatal stroke |
|
|
|
|
|
|
No. of event |
159 (3.4) |
177 (3.8) |
27 (1.6) |
44 (2.7) |
155 (2.1) |
177 (2.4) |
HR (95% CI) |
0.89 (0.72–1.11) |
|
0.61 (0.38–0.99) |
|
0.86 (0.70–1.07) |
|
P value |
0.3 |
|
0.04 |
|
|
NR |
Table 2Subgroup analysis of MACE risks according to race
Race |
Trial |
Treatment |
Placebo |
RR |
95% CI |
Event |
Total |
Incidence, % |
Event |
Total |
Incidence, % |
White |
All |
1,270 |
10,554 |
12.0 |
1,373 |
10,595 |
13.0 |
0.92 |
0.84–1.01 |
LEADER |
494 |
3,616 |
13.7 |
543 |
3,622 |
15.0 |
0.91 |
0.81–1.03 |
SUSTAIN-6 |
93 |
1,384 |
6.7 |
118 |
1,352 |
8.7 |
0.77 |
0.59–1.01 |
EXSCEL |
683 |
5,554 |
12.3 |
712 |
5,621 |
12.7 |
0.97 |
0.87–1.08 |
Black |
All |
95 |
920 |
10.3 |
128 |
956 |
13.4 |
0.78 |
0.60–0.99 |
LEADER |
47 |
370 |
12.7 |
59 |
407 |
14.5 |
0.88 |
0.60–1.29 |
SUSTAIN-6 |
5 |
108 |
4.6 |
7 |
113 |
6.2 |
0.75 |
0.24–2.35 |
EXSCEL |
43 |
442 |
9.7 |
62 |
436 |
14.2 |
0.68 |
0.46–1.01 |
Asian |
All |
72 |
1,281 |
5.6 |
147 |
1,344 |
10.9 |
0.35 |
0.09–1.32 |
LEADER |
4 |
435 |
0.9 |
56 |
465 |
12.0 |
0.08 |
0.03–0.21 |
SUSTAIN-6 |
8 |
121 |
6.6 |
17 |
152 |
11.2 |
0.59 |
0.26–1.37 |
EXSCEL |
60 |
725 |
8.3 |
74 |
727 |
10.2 |
0.81 |
0.58–1.14 |
Other |
All |
82 |
879 |
9.3 |
96 |
0819 |
11.7 |
0.78 |
0.59–1.03 |
LEADER |
27 |
211 |
12.8 |
36 |
178 |
20.2 |
0.63 |
0.38–1.04 |
SUSTAIN-6 |
2 |
35 |
5.7 |
4 |
32 |
12.5 |
0.46 |
0.08–2.50 |
EXSCEL |
53 |
633 |
8.4 |
56 |
609 |
9.2 |
0.91 |
0.63–1.33 |