Background
Methods
Study design
Objectives
Statistical analysis
Results
Participant characteristics
Characteristic | Patients without a nonfatal MI during the trial randomized to sitagliptin or placebo N = 14,055 | Patients with a nonfatal MI during the trial | P-value* | |
---|---|---|---|---|
Sitagliptin N = 289 | Placebo N = 302 | |||
Age at randomization (years)a | 65.0 (60.0, 71.0) | 67.0 (62.0, 74.0) | 66.0 (60.0, 72.0) | 0.1414 |
Female | 4161 (29.6%) | 56 (19.4%) | 75 (24.8%) | 0.1103 |
Hispanic or Latino | 1754 (12.5%) | 17 (5.9%) | 22 (7.3%) | 0.4924 |
Race | 0.4603 | |||
White | 9472 (67.4%) | 235 (81.3%) | 234 (77.5%) | |
Black | 422 (3.0%) | 10 (3.5%) | 14 (4.6%) | |
Asian | 3184 (22.7%) | 38 (13.1%) | 42 (13.9%) | |
Other | 977 (7.0%) | 6 (2.1%) | 12 (4.0%) | |
Region | 0.5023 | |||
Latin America | 1445 (10.3%) | 10 (3.5%) | 11 (3.6%) | |
Asia Pacific and other | 4377 (31.1%) | 98 (33.9%) | 84 (27.8%) | |
Western Europe | 1977 (14.1%) | 48 (16.6%) | 50 (16.6%) | |
Eastern Europe | 3822 (27.2%) | 63 (21.8%) | 68 (22.5%) | |
North America | 2434 (17.3%) | 70 (24.2%) | 89 (29.5%) | |
Durationb of type 2 diabetes (years) | 10.0 (5.0, 16.0) | 11.0 (6.0, 18.0) | 11.0 (6.0, 16.0) | 0.3233 |
Diabetes therapy at baseline (alone or in combination) | ||||
Sulfonylurea | 6394 (45.5%) | 110 (38.1%) | 125 (41.4%) | 0.4085 |
Metformin | 11,501 (81.8%) | 212 (73.4%) | 235 (77.8%) | 0.2069 |
Thiazolidinedione | 376 (2.7%) | 9 (3.1%) | 9 (3.0%) | 0.9245 |
Insulin | 3208 (22.8%) | 98 (33.9%) | 98 (32.5%) | 0.7063 |
Preexisting vascular disease | 13,975 (99.4%) | 288 (99.7%) | 302 (100.0%) | 0.4890 |
Coronary artery disease | 10,312 (73.4%) | 261 (90.3%) | 269 (89.1%) | 0.6208 |
Cerebrovascular disease | 3445 (24.5%) | 72 (24.9%) | 65 (21.5%) | 0.3289 |
Peripheral arterial disease | 2348 (16.7%) | 40 (13.8%) | 42 (13.9%) | 0.9814 |
Prior MI | 5899 (42.0%) | 171 (59.2%) | 170 (56.3%) | 0.4790 |
Prior congestive heart failure | 2511 (17.9%) | 62 (21.5%) | 61 (20.2%) | 0.7072 |
Previous atrial fibrillation/flutter | 1086 (7.7%) | 32 (11.1%) | 45 (14.9%) | 0.1670 |
NYHA classification | 0.3241 | |||
1 | 510 (20.3%) | 16 (25.8%) | 8 (13.1%) | |
2 | 1256 (50.0%) | 24 (38.7%) | 30 (49.2%) | |
3 | 339 (13.5%) | 6 (9.7%) | 10 (16.4%) | |
4 | 11 (0.4%) | 1 (1.6%) | 1 (1.6%) | |
Not available | 395 (15.7%) | 15 (24.2%) | 12 (19.7%) | |
Qualifying HbA1c (mmol/mol) | 55.2 (50.8, 60.7) | 56.1 (51.0, 61.7) | 55.2 (51.9, 59.6) | 0.3239 |
Qualifying HbA1c (%) | 7.2 (6.8, 7.7) | 7.3 (6.8, 7.8) | 7.2 (6.9, 7.6) | 0.3239 |
eGFR (mL/min/1.73 m2) | 73.0 (60.0, 88.0) | 68.5 (55.0, 84.0) | 69.0 (56.0, 88.0) | 0.2918 |
Urine albumin creatinine ratio (g/mol creatinine) | 10.6 (3.5, 35.0) | 12.2 (5.3, 52.7) | 13.8 (5.3, 43.9) | 0.9026 |
Heart rate (bpm) | 72.0 (65.0, 79.0) | 70.0 (62.0, 78.0) | 71.0 (62.0, 80.0) | 0.0595 |
Body mass index (kg/m2) | 29.5 (26.3, 33.2) | 29.8 (26.6, 33.5) | 30.4 (27.2, 34.3) | 0.1480 |
Weight (kg) | 83.0 (71.0, 96.0) | 85.0 (75.0, 98.0) | 88.5 (75.0, 100.0) | 0.1517 |
Height (cm) | 168.0 (160.0, 174.2) | 169.4 (163.2, 175.3) | 170.0 (162.6, 176.0) | 0.5036 |
Cigarette smoking status | 0.9049 | |||
Current | 1589 (11.3%) | 44 (15.2%) | 43 (14.2%) | |
Former | 5575 (39.7%) | 129 (44.6%) | 133 (44.0%) | |
Never | 6891 (49.0%) | 116 (40.1%) | 126 (41.7%) | |
Systolic blood pressure (mmHg) | 133.0 (124.0, 145.0) | 136.0 (124.0, 146.0) | 135.0 (124.0, 148.0) | 0.9803 |
Diastolic blood pressure (mmHg) | 79.0 (70.0, 84.0) | 77.0 (68.0, 82.0) | 76.0 (68.0, 85.0) | 0.3050 |
LDL-C | 84.0 (65.0, 109.0) | 81.0 (63.0, 99.6) | 82.1 (65.6, 108.1) | 0.4128 |
Medications taken at time of randomization | ||||
Statins | 11,213 (79.8%) | 238 (82.4%) | 248 (82.1%) | 0.9408 |
ACE inhibitors or angiotensin receptor blockers | 11,040 (78.5%) | 238 (82.4%) | 255 (84.4%) | 0.4959 |
Diuretics | 5727 (40.7%) | 127 (43.9%) | 150 (49.7%) | 0.1633 |
Calcium channel blockers | 4730 (33.7%) | 104 (36.0%) | 118 (39.1%) | 0.4386 |
Beta blockers | 8876 (63.2%) | 210 (72.7%) | 221 (73.2%) | 0.8881 |
Aspirin | 11,027 (78.5%) | 244 (84.4%) | 235 (77.8%) | 0.0403 |
Fatal and nonfatal MI
CV events after nonfatal MI
Sitagliptin n = 289 | Placebo n = 302 | Unadjusted hazard ratio (95% CI) | P-value | Adjusted hazard ratio (95% CI) | P-value | |||
---|---|---|---|---|---|---|---|---|
No. (%) | Events per 100 patient-years | No. (%) | Events per 100 patient-years | |||||
Cardiovascular death or hospitalization for heart failure | 58 (20.1) | 13.9 | 50 (16.6) | 11.7 | 1.21 (0.83–1.77) | 0.32 | 1.23 (0.83–1.82) | 0.31 |
Cardiovascular death | 34 (11.8) | 7.6 | 32 (10.6) | 7.1 | 1.11 (0.68–1.81) | 0.67 | 1.12 (0.67–1.86) | 0.67 |
Hospitalization for heart failure | 31 (10.7) | 7.5 | 26 (8.6) | 6.1 | 1.26 (0.75–2.12) | 0.39 | 1.40 (0.80–2.42) | 0.23 |
New onset heart failure | 19 (6.6) | 4.3 | 17 (5.6) | 3.8 | 1.25 (0.64–2.44) | 0.51 | 1.49 (0.72–3.09) | 0.28 |
Cardiovascular death, hospital admission for heart failure, new heart failure, acute myocardial infarction, stroke or new-onset atrial fibrillation | 108 (37.4) | 33.0 | 100 (33.1) | 28.4 | 1.16 (0.89–1.53) | 0.27 | 1.21 (0.91–1.60) | 0.20 |
Further acute myocardial infarction | 54 (18.7) | 7.4 | 55 (18.2) | 7.1 | 1.01 (0.69–1.48) | 0.95 | 0.99 (0.67–1.46) | 0.95 |
All-cause death | 50 (17.3) | 11.0 | 37 (12.3) | 8.1 | 1.40 (0.92–2.15) | 0.12 | 1.41 (0.90–2.21) | 0.13 |
On-treatment sensitivity analyses
DPP-4i treated n = 249 | Not DPP-4i treated n = 341 | Unadjusted hazard ratio (95% CI) | P-value | Adjusted hazard ratio (95% CI) | P-value | |||
---|---|---|---|---|---|---|---|---|
No. (%) | Events per 100 patient-years | No. (%) | Events per 100 patient-years | |||||
Cardiovascular death or hospitalization for heart failure | 45 (18.1) | 11.9 | 62 (18.2) | 13.3 | 0.91 (0.62–1.34) | 0.63 | 0.95 (0.64–1.43) | 0.82 |
Cardiovascular death | 25 (10.0) | 6.2 | 40 (11.7) | 8.1 | 0.78 (0.47–1.29) | 0.34 | 0.75 (0.44–1.26) | 0.27 |
Hospitalization for heart failure | 27 (10.8) | 7.2 | 30 (8.8) | 6.4 | 1.15 (0.68–1.94) | 0.60 | 1.34 (0.77–2.33) | 0.31 |
New onset heart failure | 16 (6.4) | 4.0 | 20 (5.9) | 4.1 | 1.05 (0.54–2.05) | 0.88 | 1.34 (0.64–2.79) | 0.44 |
Cardiovascular death, hospital admission for heart failure, new heart failure, acute myocardial infarction, stroke or new-onset atrial fibrillation | 87 (34.9) | 28.8 | 120 (35.2) | 31.8 | 0.92 (0.70–1.22) | 0.56 | 0.95 (0.71–1.27) | 0.72 |
Further acute myocardial infarction | 46 (18.5) | 7.2 | 63 (18.5) | 7.3 | 0.97 (0.66–1.42) | 0.89 | 0.99 (0.67–1.46) | 0.95 |
All-cause death | 37 (14.9) | 8.9 | 49 (14.4) | 9.9 | 0.94 (0.61–1.44) | 0.77 | 0.91 (0.58–1.43) | 0.68 |