TABLE 1.
Key cardiovascular outcomes results for selected GLP-1 receptor agonists.
| GLP-1 RA (class, regimen) | CVOT (years of follow-up) | Population | Outcomes, hazard ratio (95%CI) | |||
|---|---|---|---|---|---|---|
| N | History of heart failure (established CVD b ) | Hospitalisation for heart failure | 3-point MACE c | Kidney outcomes (Sattar et al., 2021; von Scholten et al., 2022) | ||
| Efpeglenatide (exendin-4, s.c. OW a ) | AMPLITUDE-O (31) (1.8 years) | 4,076 | 18% (90%) | 0.61 (0.38–0.98) | 0.73 (0.58–0.92) | 0.68 (0.57–0.79) |
| Lixisenatide (hGLP-1, s.c. OD a ) | ELIXA (32) (2.1 years) | 6,068 | 22% (100%) | 0.96 (0.75–1.23) | 1.02 (0.89–1.17) | 0.84 (0.68–1.02) |
| Exenatide ER (exendin-4, s.c. OW) | EXSCEL (33) (3.2 years) | 14,752 | 16% (73%) | 0.94 (0.78–1.13) | 0.91 (0.83–1.00) | 0.88 (0.76–1.01) |
| Albiglutide (hGLP-1, s.c. OD a ) | HARMONY(34) (1.5 years) | 9,463 | 20% (100%) | 0.71 (0.53–0.94) | 0.78 (0.68–0.90) | N/A |
| Liraglutide (hGLP-1, s.c. OD) | LEADER (18) (3.8 years) | 9,340 | 18% (81%) | 0.87 (0.73–1.05) | 0.87 (0.78–0.97) | 0.78 (0.67–0.92) |
| Semaglutide, oral (hGLP-1, p.o. OD) | PIONEER 6 (35) (1.3 years) d | 3,183 | 12% (85%) | 0.86 (0.48–1.55) | 0.79 (0.57–1.11) | N/A |
| Dulaglutide (hGLP-1, s.c. OW) | REWIND(17) (5.4 years) | 9,901 | 9% (31%) | 0.93 (0.77–1.12) | 0.88 (0.79–0.99) | 0.85 (0.77–0.93) |
| Semaglutide, s.c. (hGLP-1, s.c. OW) | SUSTAIN 6 (19) (2.1 years) | 3,297 | 24% (83%) | 1.11 (0.77–1.61) | 0.74 (0.58–0.95) | 0.64 (0.46–0.88) |
| Meta-analysis | 0.89 (0.82 to 0.98) (Sattar et al., 2021) | 0.86 (0.80–0.93) (Sattar et al., 2021) | 0.79 (0.73–0.87) (Sattar et al., 2021) | |||
CI, confidence interval; CVD; cardiovascular disease; CVOT, cardiovascular outcomes trial; GLP-1, glucagon-like peptide-1; hGLP-1, GLP-1, receptor agonist based on human GLP-1; MACE, major adverse cardiovascular event; OD, once-daily dosing; OW, once-weekly dosing; p.o., per oral administration in a tablet; RA, receptor agonist; s.c., subcutaneous injection.
not marketed.
trials enrolled people with established cardiovascular disease and/or elevated cardiovascular risk factors (see original publications).
primary 3-point composite outcome (first occurrence of either cardiovascular death, myocardial infarction, or stroke; in ELIXA, also hospital admission for unstable angina).
PIONEER, 6 was designed to document cardiovascular safety only.