TABLE 7.
Summary of the GLP-1RA Cardiovascular Outcomes Trials
| LEADER (10) | SUSTAIN-6* (11) | EXSCEL (58) | ELIXA (59) | |
|---|---|---|---|---|
| Patients enrolled | 9,340 | 3,297 | 14,752 | 6,068 |
| Drug | Liraglutide | Semaglutide | Exenatide QW | Lixisenatide |
| Dose | 1.8 mg or max tolerated dose per day | 0.5 mg or 1 mg per week | 2 mg per week | 10 mcg or 20 mcg per day |
| Duration of follow up (years) | 3.8 | 2.1 | 3.2 | 2.1 |
| Baseline A1C | 8.7 | 8.7 | 8.0 | 7.7 |
| Mean duration of diabetes (years) | 12.8 | 13.9 | 12 | 9.3 |
| Baseline metformin use (%) | 76 | 73 | 77 | 66 |
| Baseline statin use (%) | 72 | 73 | 74 | 93 |
| Baseline prevalence of CV disease†/HF (%) | 81/18 | 72/24 | 73.1/16.2 | 100/22 |
| Primary outcome, HR (95% CI)‡ | 3-point MACE 0.87 (0.78-0.97) | 3-point MACE 0.74 (0.58-0.95) | 3-point MACE 0.91 (0.83-1.00) | 4-point MACE 1.02 (0.89-1.17) |
| CV death, HR (95% CI) | 0.78 (0.66-0.93) | 0.98 (0.65-1.48) | 0.88 (0.76-1.02) | 0.98 (0.78-1.22) |
| Fatal or nonfatal MI, HR (95% CI)§ | 0.86 (0.73-1.00) | 0.74 (0.51-1.08) | 0.97 (0.85-1.10) | 1.03 (0.87-1.22) |
| Fatal or nonfatal stroke, HR (95% CI)§ | 0.86 (0.71-1.06) | 0.61 (0.38-0.99) | 0.85 (0.70-1.03) | 1.12 (0.79-1.58) |
| All-cause mortality, HR (95% CI) | 0.85 (0.74-0.97) | 1.05 (0.74-1.50) | 0.86 (0.77-0.97) | 0.94 (0.78-1.13) |
| HF hospitalization, HR (95% CI) | 0.87 (0.73-1.05) | 1.11 (0.77-1.61) | 0.94 (0.78-1.13) | 0.96 (0.75-1.23) |
As noted in the text, SUSTAIN-6 was designed and powered as a noninferiority trial. Testing for superiority for the primary CV outcome was not prespecified.
SUSTAIN-6 reported that 72.2% of patient had established CV disease with or without chronic kidney disease, and 10.7% had chronic kidney disease without cardiovascular disease. In total, 83% had established CV disease including chronic kidney disease of stage 3 or higher.
Three-point MACE is a composite of CV death, myocardial infarction, or stroke. The 4-point MACE used in the ELIXA trial the composite of CV death, myocardial infarction, stroke, or hospitalization for unstable angina.
The risk estimates and 95% CI for SUSTAIN-6 and ELIXA are for nonfatal MI (excluding fatal MI) or nonfatal stroke (excluding fatal stroke). The effect estimates for the composite endpoints of fatal or nonfatal MI and fatal or nonfatal stroke were not available in the primary manuscripts.
A1C = hemoglobin A1C; CV = cardiovascular; ELIXA = Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome; EXSCEL =Exenatide Study of Cardiovascular Event Lowering; GLP-RA = glucagon-like peptide-1 receptor agonists; HF = heart failure; MACE = major adverse cardiovascular event; MI = myocardial infarction; QW = once weekly; LEADER =The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6 = Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.