Table 1: Overview of Cardiovascular Outcome Trials with Glucose-lowering Therapies.
| Agent | Trial | Population | n | Median Follow-up (Years) | MACE Outcome, HR [95% CI] |
|---|---|---|---|---|---|
| Dipeptidyl Peptidase-4 Inhibitors | |||||
| Saxagliptin | SAVOR | Age ≥40 years with ASCVD; ≥55 years men or ≥60 years women with ≥1 CV risk factor | 16,492 | 2.1 | HR 1.00 [0.89–1.12] |
| Alogliptin | EXAMINE | Age ≥18 years with recent ACS | 5,380 | 1.5 | HR 0.96 [≤1.16] |
| Sitagliptin | TECOS | Age ≥50 years with ASCVD | 14,671 | 3.0 | HR 0.98 [0.88–1.09] |
| Linagliptin | CARMELINA | History of ASCVD and micro- or macro-albuminuria | 6,979 | 2.2 | HR 1.02 [0.89–1.17] |
| Linagliptin | CAROLINA* | ASCVD; ≥2 CV risk factors; age ≥70 years and microvascular complications | 6,042 | 6.3 | HR 0.98 [0.84–1.14] |
| Glucagon-like Peptide-1 Receptor Agonists | |||||
| Lixisenatide | ELIXA | Age ≥30 years with ASCVD | 6,068 | 2.1 | HR 1.02 [0.89–1.17] |
| Liraglutide | LEADER | Age ≥50 years with ASCVD; age ≥60 years with ≥1 CV risk factor | 9,340 | 3.8 | HR 0.87 [0.78–0.97] |
| Semaglutide | SUSTAIN-6 | Age ≥50 years with ASCVD; CHF or stage 3–5 CKD; age ≥60 years with ≥1 CV risk factor | 3,297 | 2 | HR 0.74 [0.58–0.95] |
| Semaglutide (oral) | PIONEER-6 | Age ≥50 years with ASCVD or CKD; ≥60 years with ≥1 CV risk factor | 3,183 | 1.3 | HR 0.79 [0.57–1.11] |
| Exenatide XR | EXSCEL | 73% had ASCVD | 14,752 | 3.2 | HR 0.91 [0.83–1.00] |
| Albiglutide† | Harmony Outcomes | Age ≥40 years with ASCVD | 9,463 | 1.6 | HR 0.78 [0.68–0.90] |
| Dulaglitide | REWIND | Age ≥50 years with ASCVD, age ≥55 years with ASCVD or 1 CV risk factor; age ≥60 years with ≥2 CV risk factors | 9,901 | 5.4 | HR 0.88 [0.79–0.99] |
| Sodium–Glucose Cotransporter 2 Inhibitors | |||||
| Empagliflozin | EMPA-REG OUTCOME | Age ≥18 years with ASCVD | 7,020 | 3.1 | HR 0.86 [0.744–0.99] |
| Canagliflozin | CANVAS | Age ≥30 years with ASCVD; age ≥50 years with ≥2 risk factors | 10,142 | 3.6‡ | HR 0.86 [0.75–0.97] |
| Canagliflozin | CREDENCE | eGFR 30–90 and albumin:creatinine ratio >300 | 4,401 | 2.6 | HR 0.70 [0.59–0.82] |
| Dapagliflozin | DECLARE | Age ≥40 years with. ASCVD; age ≥55 years men with ≥2 CV risk factors; age ≥60 years women with ≥1 CV risk factor | 17,160 | 4.2 | HR 0.93 [0.84–1.03] |
| Dapagliflozin | DAPA-HF | NYHA class II–IV HF with LVEF ≤40% | 4,744 | 1.5 | HR 0.74 [0.65–0.85] |
| Ertugliflozin | VERTIS-CV | Age ≥40 years with ASCVD | 9,463 | 1.6 | HR 0.95 [0.85–1.11] |
*Compared with glimepiride; all other trials are compared with placebo. †Removed from the market by the manufacturer due to poor penetration. ‡Data expressed as the mean. ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; CHF = congestive heart failure; CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated glomerular filtration rate; HF = heart failure; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association.