Table 2.
Summary of major randomized trials exploring the effect of GLP-1 receptor agonists on cardiovascular outcomes.
| Parameter | CV Outcome Trials | |||||||
|---|---|---|---|---|---|---|---|---|
| ELIXA | LEADER | SUSTAIN-6 | EXSCEL | HARMONY | PIONEER 6 | REWIND | AMPLITUDE-0 | |
| Year | 2015 | 2016 | 2016 | 2017 | 2018 | 2019 | 2019 | 2021 |
| Patient characteristics | T2DM with a recent acute coronary event | T2DM at high CV risk | T2DM at high CV risk | T2DM with and without established CV disease | T2DM and CV disease | T2DM at high CV risk | T2DM with and without established CV disease | T2DM and either history of CV disease or current CKD |
| N | 6068 | 9340 | 3297 | 14,752 | 9463 | 3183 | 9901 | 4076 |
| GLP1-RA | Lixisenatide | Liraglutide | Semaglutide | Exenatide | Albiglutide | Semaglutide | Dulaglutide | Efpeglenatide |
| Median follow-up (years) | 2.1 | 3.8 | 2.1 | 3.2 | 1.6 | 1.3 | 5.4 | 1.8 |
| eGFR (mL/min/1.73 m2) | 76 | 80 | 80 | 76 | 79 | 74 | 75 | 72 |
| eGFR < 60 mL/min/1.73 m2 (%) | 25 | 25 | 29 | 22 | 23 | 27 | 22 | 32 |
| UACR < 30 mg/g (%) | 74 | 64 | NA | 79 | NA | 67 | 65 | 54 |
| UACR 30–300 mg/g (%) | 19 | 26 | NA | 17 | NA | 33 * | 27 | 46 * |
| UACR > 300 mg/g (%) | 7 | 10 | NA | 4 | NA | - | 8 | NA |
| Baseline ACEI or ARB use (%) | 85 | 83 | 84 | 80 | 82 | NA | 81 | 79 |
| Primary outcome | CV death, MI, stroke or hospitalization for unstable angina | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke | CV death, non-fatal MI, non-fatal stroke |
| HR (95% CI) | 1.02 (0.89–1.17) | 0.87 (0.78–0.97) | 0.74 (0.58–0.95) | 0.91 (0.83–1.00) | 0.78 (0.68–0.90) | 0.79 (0.57–1.11) | 0.88 (0.79–0.99) | 0.73 (0.58–0.92) |
Abbreviations: ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval; CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated-glomerular-filtration-rate; GLP1-RA = glucagon-like peptide-1 receptor agonist; HR = hazard ratio; MI = myocardial infarction; NA = not available; T2DM = diabetes mellitus type 2; UACR = urinary albumin-to-creatinine ratio. * Combination of UACR 30–300 mg/g and UACR >300 mg/g.