Table 2 Characteristics of GLP-1RA trials [100, 135–138]
| Â | EXSCEL | ELIXA | LEADER | SUSTAIN-6 | HARMONY | REWIND |
|---|---|---|---|---|---|---|
GLP-1RA | Exenatide | Lixisenatide | Liraglutide | Semaglutide (SC) | Albiglutide | Dulaglutide |
N | 14,752 | 6068 | 9340 | 3297 | 9463 | 9901 |
Inclusion criteria | T2DM With prior cardiovascular events and/or with or without known cardiovascular risk factors | T2DM Acute coronary event within 180Â days prior to randomization | T2DM Previous CVD or CKD High risk CVD | T2DM Previous CVD or CKD High-risk CVD | T2DM Previous CVD High-risk CVD | T2DM Previous CVD High-risk CVD |
Study design | Phase 3/4 multicentre, randomised, double-blind, placebo-controlled, parallel-group; non-inferiority, superiority (hierarchical analysis) | Multicentre, randomised, double-blind, placebo-controlled; non-inferiority, superiority | Multicentre, double-blind, placebo-controlled; non-inferiority, superiority (hierarchical analysis) | Multicentre, double-blind, placebo-controlled; non-inferiority, superiority testing was not part of the pre-specified analysis | Multicentre, randomised, double-blind, placebo-controlled; non-inferiority, superiority testing was pre-specified | Multicentre, randomised, double-blind, placebo-controlled; non-inferiority, superiority testing was pre-specified |
Primary outcome | 3-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke | 4-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke, hospitalisation for unstable angina | 3-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke | 3-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke | 3-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke | 3-point MACE: cardiovascular death, non-fatal MI, non-fatal stroke |
Results | Exenatide group: 11.4% Placebo group: 12.2% HR 0.91; 95% CI 0.83–1.00 P < 0.001 for non-inferiority, P = 0.06 for superiority | Lixisenatide group: 13.4% Placebo group: 13.2% HR 1.02; 95% CI 0.89–1.17 P < 0.001 for non-inferiority, P = 0.81 for superiority | Liraglutide group: 13.0% Placebo group: 14.9% HR 0.87; 95% CI 0.78–0.97 P < 0.001 for non-inferiority, P = 0.01 for superiority | Semaglutide group: 6.6% Placebo group: 8.9% HR 0.74; 95% CI 0.58–0.95 P < 0.001 for non-inferiority, P = 0.02 for superiority | Albiglutide group: 7.1% Placebo group: 9.0% HR 0.78; 95% CI 0.68–0.90 P < 0.001 for non-inferiority, P = 0.0006 for superiority | Preliminary results reported as a positive trial |
Additional findings |  |  | Reduction in all-cause mortality in the liraglutide group (8.2% vs. 9.6% in placebo group; HR 0.85; 95% CI 0.74–0.97; P = 0.02) Reduction in CV death in the liraglutide group (4.7% vs. 6.0% in the placebo group; HR 0.78; 95% CI 0.66–0.93; P = 0.007) | Reduction in nonfatal stroke: Semaglutide group: 1.6% Placebo group: 2.7% HR 0.61; 95% CI, 0.38–0.99 P = 0.04 |  |  |