Table 3.
Characteristics of twelve trials that evaluated cardiovascular safety in patients with type 2 diabetes
| Trial | Drug (Class) | No. of subjects | Age, y | Men % | BMI | Baseline HbA1c, % | Median follow‐up period, y | Primary endpoint | Primary endpointa | HbA1c achieved, % | Adverse eventsb |
|---|---|---|---|---|---|---|---|---|---|---|---|
| EXAMINE83, 84 | Alogliptin (DPP‐4) | 5380 | 61.0 | 68.0 | 28.7 | 8.0 | 1.5 | 3 MACE | 0.96 (≤1.16) | <7 | Heart failure |
| CARMELINA85 | Linagliptin (DPP‐4) | 6979 | 66.1 | 61.5 | 31.4 | 8.0 | 2.2 | 3 MACE | 1.02 (0.89‐1.17) | <7.4 | |
| SAVOR‐TIMI86 | Saxagliptin (DPP‐4) | 16 492 | 65.1 | 66.6 | 31.1 | 8.0 | 2.1 | 3 MACE | 1.00 (0.98‐1.12) | <7.5 | Heart failure |
| TECOS87 | Sitagliptin (DPP‐4) | 14 671 | 65.4 | 70.9 | 30.2 | 7.2 | 3.0 | 4 MACE | 0.98 (0.89‐1.08) | <6.8 | |
| HARMONY88 | Albiglutide (GLP‐1) | 9463 | 64.1 | 70.0 | 32.3 | 8.7 | 1.6 | 3 MACE | 0.78 (0.68‐0.90) | <7.7 | |
| EXSCEL89 | Exenatide (GLP‐1) | 14 752 | 62.0 | 62.0 | 31.8 | 8.0 | 3.2 | 3 MACE | 0.91 (0.83‐1.00) | <7.2 | |
| LEADER90 | Liraglutide (GLP‐1) | 9340 | 64.2 | 64.5 | 32.5 | 8.7 | 3.8 | 3 MACE | 0.87 (0.78‐0.97) | <7 | |
| ELIXA91 | Lixisenatide (GLP‐1) | 6068 | 59.9 | 69.6 | 30.1 | 7.7 | 2.1 | 4 MACE | 1.02 (0.89‐1.17) | <7 | |
| SUSTAIN‐692 | Semaglutide (GLP‐1) | 3297 | 64.7 | 61.5 | 32.8 | 8.7 | 2.1 | 3 MACE | 0.74 (0.58‐0.95) | <6.8 | |
| CANVAS93 | Canagliflozin (SGLT2) | 10 142 | 63.2 | 64.9 | 31.9 | 8.2 | 3.6 | 3 MACE | 0.86 (0.75‐0.97) | <7.5 | Amputation |
| DECLARE‐TIMI94 | Dapagliflozin (SGLT2) | 17 160 | 63.9 | 63.1 | 32.1 | 8.3 | 4.2 | 3 MACE | 0.93 (0.84‐1.03) | <7.6 | |
| EMPA‐REG OUTCOME95, 96 | Empagliflozin (SGLT2) | 7028 | 63.1 | 71.2 | 30.6 | 8.1 | 3.1 | 3 MACE | 0.86 (0.74‐0.99) | <7.3 |
BMI, body mass index; CANVAS, Canagliflozin Cardiovascular Assessment Study; CARMELINA, Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; CI, confidence interval; DECLARE‐TIMI, Dapagliflozin Effect on Cardiovascular Events‐Thrombolysis in Myocardial Infarction; DPP‐4, dipeptidyl peptidase‐4 inhibitor; ELIXA, Evaluation of Lixisenatide in Acute Coronary Syndrome; EMPA‐REG OUTCOME, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; EXAMINE, Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care; EXSCEL, Exenatide Study of Cardiovascular Event Lowering; GLP‐1, glucagon‐like peptide 1 receptor agonist; HARMONY, Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease; HbA1c, glycated hemoglobin A1c; HR, hazard ratio; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; 3 MACE, three‐component major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke); 4 MACE, four‐component major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina); P, placebo; SAVOR‐TIMI, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus‐Thrombolysis in Myocardial Infarction; SGLT2, sodium glucose cotransporter 2 inhibitor; SUSTAIN 6, Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes; TECOS, Trial Evaluating Cardiovascular Outcomes with Sitagliptin.
Data are presented as the hazard ratio (95% confidence interval).
Adverse events were significantly more frequent in the test drug group.