Background
Methods
Data source
Patient enrollment and exclusion criteria
Exposure of linagliptin
Outcomes and covariate measurements
Characteristics | Before matching | After matching | |||
---|---|---|---|---|---|
Linagliptin (n = 401) | Control (n = 17,227) |
P
| Control (n = 802) |
P
| |
Age, years | 69.6 ± 10.9 | 70.0 ± 11.1 | .525 | 69.1 ± 11.3 | .415 |
Age ≥ 75 years | 143 (35.7) | 6216 (36.1) | .862 | 263 (32.8) | .321 |
Gender | .081 | .744 | |||
Male | 216 (53.9) | 10,029 (58.2) | 424 (52.9) | ||
Female | 185 (46.1) | 7198 (41.8) | 378 (47.1) | ||
T2DM duration, years | 12.9 ± 3.5 | 11.7 ± 3.9 | < .001 | 12.8 ± 3.4 | .922 |
T2DM duration group (years) | < .001 | .825 | |||
0–5 | 20 (5.0) | 1508 (8.8) | 38 (4.7) | ||
6–10 | 54 (13.5) | 3064 (17.8) | 121 (15.1) | ||
11–15 | 212 (52.9) | 9425 (54.7) | 405 (50.5) | ||
> 15 | 115 (28.7) | 3230 (18.8) | 238 (29.7) | ||
Comorbidity | |||||
Old myocardial infarction | 45 (11.2) | 1524 (8.8) | .099 | 83 (10.3) | .643 |
Old ischemic stroke | 101 (25.2) | 4837 (28.1) | .203 | 229 (28.6) | .217 |
Heart failure | 70 (17.5) | 2467 (14.3) | .077 | 129 (16.1) | .546 |
Venous thromboembolism | 11 (2.7) | 241 (1.4) | .025 | 21 (2.6) | .899 |
Chronic kidney disease (CKD) | < .001 | .469 | |||
None | 207 (51.6) | 11,642 (67.6) | 444 (55.4) | ||
Non-dialysis CKD | 161 (40.2) | 4479 (26.0) | 298 (37.1) | ||
Dialysis | 33 (8.2) | 1106 (6.4) | 60 (7.5) | ||
Gout | 34 (8.5) | 1506 (8.7) | .854 | 70 (8.7) | .885 |
Atrial fibrillation | 35 (8.7) | 1521 (8.8) | .944 | 54 (6.7) | .213 |
Peripheral arterial disease | 28 (7.0) | 1058 (6.1) | .489 | 59 (7.4) | .813 |
Hypertension | 337 (84.0) | 13,851 (80.4) | .069 | 682 (85.0) | .650 |
Dyslipidemia | 186 (46.4) | 6534 (37.9) | .001 | 350 (43.6) | .367 |
COPD | 30 (7.5) | 1534 (8.9) | .322 | 63 (7.9) | .819 |
Malignancy | 25 (6.2) | 1269 (7.4) | .390 | 58 (7.2) | .520 |
Cirrhosis | 8 (2.0) | 356 (2.1) | .921 | 16 (2.0) | 1.000 |
Autoimmune disease | 15 (3.7) | 280 (1.6) | .001 | 34 (4.2) | .680 |
Previous treatment | |||||
PCI | 58 (14.5) | 2110 (12.2) | .182 | 112 (14.0) | .815 |
CABG | 18 (4.5) | 419 (2.4) | .009 | 36 (4.5) | 1.000 |
Characteristics | Before matching | After matching | |||
---|---|---|---|---|---|
Linagliptin (n = 401) | Control (n = 17,227) |
P
| Control (n = 802) |
P
| |
Non-DM medication | |||||
Aspirin | 341 (85.0) | 14,549 (84.5) | .750 | 682 (85.0) | 1.000 |
Clopidogrel | 206 (51.4) | 6696 (38.9) | < .001 | 393 (49.0) | .439 |
Warfarin | 24 (6.0) | 1096 (6.4) | .760 | 47 (5.9) | .931 |
NOAC | 4 (1.0) | 197 (1.1) | .785 | 8 (1.0) | 1.000 |
ACEI/ARB | 275 (68.6) | 10,829 (62.9) | .019 | 548 (68.3) | .930 |
β-blocker | 208 (51.9) | 7388 (42.9) | < .001 | 421 (52.5) | .838 |
CCB | 209 (52.1) | 8963 (52.0) | .971 | 431 (53.7) | .595 |
Digoxin | 20 (5.0) | 957 (5.6) | .623 | 45 (5.6) | .652 |
Statin | 218 (54.4) | 8048 (46.7) | .002 | 443 (55.2) | .774 |
NSAID | 99 (24.7) | 4321 (25.1) | .857 | 208 (25.9) | .640 |
Cox-2 inhibitor | 28 (7.0) | 1493 (8.7) | .235 | 54 (6.7) | .871 |
Diuretic | 116 (28.9) | 3528 (20.5) | < .001 | 217 (27.1) | .494 |
Spironolactone | 35 (8.7) | 1355 (7.9) | .526 | 65 (8.1) | .712 |
Fibrate | 32 (8.0) | 1242 (7.2) | .556 | 72 (9.0) | .562 |
DM medication | |||||
Biguanide | 156 (38.9) | 8177 (47.5) | .001 | 331 (41.3) | .430 |
Sulfonylurea | 204 (50.9) | 6864 (39.8) | < .001 | 445 (55.5) | .130 |
Thiazolidinedione | 27 (6.7) | 869 (5.0) | .128 | 47 (5.9) | .553 |
Alpha-glucosidase inhibitor | 81 (20.2) | 2037 (11.8) | < .001 | 165 (20.6) | .879 |
Non-SU insulin secretagogue (Glinide) | 93 (23.2) | 2397 (13.9) | < .001 | 164 (20.4) | .274 |
Insulin | 244 (60.8) | 7807 (45.3) | < .001 | 484 (60.3) | .868 |
Statistical analysis
Results
Study patients
Baseline characteristics
Primary outcomes
Outcome | Number of event (%) | Linagliptin vs. control | ||
---|---|---|---|---|
Linagliptin (n = 154) | Control (n = 308) | HR (95% CI) |
P
| |
Primary outcomes | ||||
6 month follow-up | ||||
Cardiovascular death | 5 (3.2) | 11 (3.6) | .83 (.29, 2.40) | .735 |
Non-fatal myocardial infarction | 6 (3.9) | 8 (2.6) | 1.38 (.48, 3.99) | .547 |
Non-fatal ischemic stroke | 1 (.6) | 3 (1.0) | .62 (.06, 5.95) | .678 |
Primary composite outcomea | 10 (6.5) | 22 (7.1) | .84 (.40, 1.78) | .648 |
At the end of follow-up | ||||
Cardiovascular death | 8 (5.2) | 13 (4.2) | 1.13 (.47, 2.73) | .781 |
Non-fatal myocardial infarction | 7 (4.5) | 10 (3.2) | 1.29 (.49, 3.38) | .610 |
Non-fatal ischemic stroke | 3 (1.9) | 3 (1.0) | 1.89 (.38, 9.34) | .438 |
Primary composite outcomea | 15 (9.7) | 26 (8.4) | 1.08 (.57, 2.03) | .821 |
Secondary outcomes | ||||
All-cause mortality | 13 (8.4) | 23 (7.5) | 1.07 (.54, 2.12) | .840 |
Other cardiovascular outcomes | ||||
Hospitalization for heart failure | 16 (10.4) | 22 (7.1) | 1.41 (.74, 2.69) | .292 |
Percutaneous coronary intervention | 23 (14.9) | 30 (9.7) | 1.48 (.86, 2.54) | .160 |
Coronary artery bypass grafting | 4 (2.6) | 6 (1.9) | 1.25 (.35, 4.44) | .727 |
Safety outcomes | ||||
Hypoglycemia | 6 (3.9) | 8 (2.6) | 1.43 (.50, 4.12) | .509 |
DKA or HHS | 1 (.6) | 2 (.6) | .96 (.09, 10.54) | .970 |
Acute pancreatitis | 0 (.0) | 0 (.0) | NA | NA |
De novo dialysis | 10 (6.5) | 16 (5.2) | 1.31 (.59, 2.89) | .512 |
Acute hepatitis | 2 (1.3) | 0 (.0) | NA | NA |
Newly diagnosed malignancy | 1 (.6) | 5 (1.6) | .38 (.04, 3.25) | .377 |
Outcome | Number of event (%) | Linagliptin vs. control | ||
---|---|---|---|---|
Linagliptin (n = 239) | Control (n = 478) | HR (95% CI) |
P
| |
Primary outcomes | ||||
6 month follow-up | ||||
Cardiovascular death | 4 (1.7) | 9 (1.9) | .85 (.26, 2.75) | .782 |
Non-fatal myocardial infarction | 0 (.0) | 0 (.0) | NA | NA |
Non-fatal ischemic stroke | 6 (2.5) | 24 (5.0) | .47 (.19, 1.14) | .095 |
Primary composite outcomea | 10 (4.2) | 33 (6.9) | .57 (.28, 1.15) | .114 |
At the end of follow-up | ||||
Cardiovascular death | 4 (1.7) | 10 (2.1) | .77 (.24, 2.46) | .658 |
Non-fatal myocardial infarction | 0 (.0) | 0 (.0) | NA | NA |
Non-fatal ischemic stroke | 7 (2.9) | 27 (5.6) | .49 (.21, 1.12) | .089 |
Primary composite outcomea | 11 (4.6) | 36 (7.5) | .57 (.29, 1.12) | .104 |
Secondary outcomes | ||||
All-cause mortality | 9 (3.8) | 21 (4.4) | .88 (.40, 1.92) | .742 |
Other cardiovascular outcomes | ||||
Hospitalization for heart failure | 4 (1.7) | 7 (1.5) | 1.14 (.33, 3.88) | .839 |
Percutaneous coronary intervention | 3 (1.3) | 4 (.8) | 1.45 (.32, 6.47) | .628 |
Coronary artery bypass grafting | 0 (.0) | 0 (.0) | NA | NA |
Safety outcomes | ||||
Hypoglycemia | 10 (4.2) | 18 (3.8) | 1.10 (.51, 2.38) | .811 |
DKA or HHS | 2 (.8) | 3 (.6) | 1.33 (.22, 7.97) | .754 |
Acute pancreatitis | 0 (.0) | 0 (.0) | NA | NA |
De novo dialysis | 8 (3.3) | 17 (3.6) | 1.20 (.50, 2.86) | .679 |
Acute hepatitis | 0 (.0) | 1 (.2) | NA | NA |
Newly diagnosed malignancy | 7 (2.9) | 14 (2.9) | 1.32 (.52, 3.39) | .561 |