Table 1.
Selected baseline characteristics of study participants after propensity-score-matching in first and sixth predefined sequential analysis
| May 2011 - June 2013 | May 2011 - December 2015 | May 2011 - June 2013 | May 2011 - December 2015 | May 2011 - June 2013 | May 2011 - December 2015 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Linagliptin | Other DPP-4i | Linagliptin | Other DPP-4i | Linagliptin | Pioglitazone | Linagliptin | Pioglitazone | Linagliptin | Sulfonylureas | Linagliptin | Sulfonylureas | |
| (N=14379) | (N=14379) | (N=31492) | (N=31492) | (N=9966) | (N=9966) | (N=23316) | (N=23316) | (N=8895) | (N=8895) | (N=19731) | (N=19731) | |
| Claims-based patient characteristics | N % or Mean (SD) | N % or Mean (SD) | N % or Mean (SD) | |||||||||
| Demographics | ||||||||||||
| Age (mean, SD) | 54.78 (11.05) | 54.80 (11.03) | 55.61 (11.70) | 55.59 (11.69) | 54.20 (11.05) | 54.23 (11.00) | 55.27 (11.74) | 55.23 (11.64) | 53.84 (11.06) | 53.83 (10.98) | 54.65 (11.65) | 54.63 (11.67) |
| Female | 5793 (40.29) | 5742 (39.93) | 12812 (40.68) | 12840 (40.77) | 4051 (40.65) | 3980 (39.94) | 9504 (40.76) | 9414 (40.38) | 3668 (41.24) | 3600 (40.47) | 8162 (41.37) | 8123 (41.17) |
| Features of medication initiation | ||||||||||||
| Monotherapy | 3790 (26.36) | 3731 (25.95) | 7469 (23.72) | 7468 (23.71) | 2867 (28.77) | 2872 (28.82) | 5961 (25.57) | 6003 (25.75) | 3188 (35.84) | 3163 (35.56) | 6340 (32.13) | 6328 (32.07) |
| Dual therapy | 6428 (44.70) | 6503 (45.23) | 14523 (46.12) | 14575 (46.28) | 4598 (46.14) | 4626 (46.42) | 11030 (47.31) | 10981 (47.10) | 4750 (53.40) | 4763 (53.55) | 10930 (55.40) | 10978 (55.64) |
| Therapy with > 2 agents | 4161 (28.94) | 4145 (28.83) | 9500 (30.17) | 9449 (30.00) | 2501 (25.10) | 2468 (24.76) | 6325 (27.13) | 6332 (27.16) | 957 (10.76) | 969 (10.89) | 2461 (12.47) | 2425 (12.29) |
| Dual therapy with metformin | 4535 (31.54) | 4558 (31.70) | 10360 (32.90) | 10357 (32.89) | 3398 (34.10) | 3396 (34.08) | 8150 (34.95) | 8018 (34.39) | 4073 (45.79) | 4100 (46.09) | 9351 (47.39) | 9478 (48.04) |
| Concomitant initiation of other antidiabetic agents | 1580 (10.99) | 1630 (11.34) | 4744 (15.06) | 4801 (15.25) | 1318 (13.22) | 1328 (13.33) | 3677 (15.77) | 3540 (15.18) | 1142 (12.84) | 1141 (12.83) | 3336 (16.91) | 3255 (16.50) |
| Concomitant initiation of metformin | 1221 (8.49) | 1250 (8.69) | 3499 (11.11) | 3539 (11.24) | 1068 (10.72) | 1076 (10.80) | 2934 (12.58) | 2805 (12.03) | 1028 (11.56) | 1020 (11.47) | 2845 (14.42) | 2805 (14.22) |
| Concomitant initiation of insulin | 133 (0.92) | 127 (0.88) | 336 (1.07) | 342 (1.09) | 104 (1.04) | 97 (0.97) | 251 (1.08) | 261 (1.12) | 81 (0.91) | 81 (0.91) | 222 (1.13) | 226 (1.15) |
| Current use of other antidiabetic agents | 9391 (65.31) | 9450 (65.72) | 20681 (65.67) | 20701 (65.73) | 14540 (62.36) | 14599 (62.61) | 4694 (52.77) | 4744 (53.33) | 10606 (53.75) | 10687 (54.16) | ||
| Current use of metformin | 7093 (49.33) | 7049 (49.02) | 15445 (49.04) | 15387 (48.86) | 4707 (47.23) | 4708 (47.24) | 11097 (47.59) | 11216 (48.10) | 3946 (44.36) | 3988 (44.83) | 8795 (44.57) | 8901 (45.11) |
| Current use of insulin | 1026 (7.14) | 1043 (7.25) | 2577 (8.18) | 2606 (8.28) | 704 (7.06) | 714 (7.16) | 1822 (7.81) | 1844 (7.91) | 656 (7.37) | 629 (7.07) | 1700 (8.62) | 1639 (8.31) |
| Comorbidities at Baseline | ||||||||||||
| Charlson comorbidity score (mean, SD) | 1.36 (0.90) | 1.37 (0.90) | 1.47 (1.01) | 1.47 (1.01) | 1.29 (0.79) | 1.28 (0.79) | 1.39 (0.91) | 1.38 (0.89) | 1.31 (0.84) | 1.32 (0.85) | 1.42 (0.96) | 1.42 (0.96) |
| Diabetic nephropathy | 594 (4.13) | 619 (4.30) | 1741 (5.53) | 1788 (5.68) | 329 (3.30) | 316 (3.17) | 1147 (4.92) | 1171 (5.02) | 290 (3.26) | 289 (3.25) | 889 (4.51) | 871 (4.41) |
| Diabetic retinopathy | 424 (2.95) | 449 (3.12) | 1081 (3.43) | 1106 (3.51) | 253 (2.54) | 252 (2.53) | 694 (2.98) | 711 (3.05) | 207 (2.33) | 212 (2.38) | 560 (2.84) | 578 (2.93) |
| Diabetic neuropathy | 832 (5.79) | 835 (5.81) | 2279 (7.24) | 2252 (7.15) | 538 (5.40) | 534 (5.36) | 1612 (6.91) | 1575 (6.76) | 417 (4.69) | 419 (4.71) | 1231 (6.24) | 1272 (6.45) |
| Peripheral vascular disease | 206 (1.43) | 224 (1.56) | 502 (1.59) | 526 (1.67) | 125 (1.25) | 124 (1.24) | 305 (1.31) | 313 (1.34) | 113 (1.27) | 101 (1.14) | 285 (1.44) | 269 (1.36) |
| Erectile dysfunction | 343 (2.39) | 330 (2.30) | 721 (2.29) | 713 (2.26) | 216 (2.17) | 212 (2.13) | 504 (2.16) | 516 (2.21) | 203 (2.28) | 193 (2.17) | 410 (2.08) | 409 (2.07) |
| Diabetic foot | 128 (0.89) | 118 (0.82) | 327 (1.04) | 305 (0.97) | 75 (0.75) | 73 (0.73) | 206 (0.88) | 203 (0.87) | 61 (0.69) | 56 (0.63) | 186 (0.94) | 187 (0.95) |
| Skin infections | 636 (4.42) | 640 (4.45) | 1406 (4.46) | 1368 (4.34) | 429 (4.30) | 419 (4.20) | 1004 (4.31) | 969 (4.16) | 390 (4.38) | 413 (4.64) | 886 (4.49) | 940 (4.76) |
| Hypoglycemia | 910 (6.33) | 893 (6.21) | 2352 (7.47) | 2270 (7.21) | 587 (5.89) | 577 (5.79) | 1684 (7.22) | 1628 (6.98) | 526 (5.91) | 544 (6.12) | 1360 (6.89) | 1421 (7.20) |
| Hypertension | 5434 (37.79) | 5421 (37.70) | 12441 (39.51) | 12438 (39.50) | 3536 (35.48) | 3532 (35.44) | 8627 (37.00) | 8669 (37.18) | 3214 (36.13) | 3245 (36.48) | 7484 (37.93) | 7457 (37.79) |
| Hyperlipidemia | 4731 (32.90) | 4723 (32.85) | 10830 (34.39) | 10802 (34.30) | 3115 (31.26) | 3082 (30.93) | 7671 (32.90) | 7714 (33.08) | 2809 (31.58) | 2801 (31.49) | 6479 (32.84) | 6502 (32.95) |
| Coronary atherosclerosis | 1201 (8.35) | 1198 (8.33) | 2841 (9.02) | 2842 (9.02) | 717 (7.19) | 731 (7.33) | 1743 (7.48) | 1746 (7.49) | 675 (7.59) | 693 (7.79) | 1662 (8.42) | 1657 (8.40) |
| Acute myocardial infarction | 116 (0.81) | 111 (0.77) | 314 (1.00) | 322 (1.02) | 51 (0.51) | 55 (0.55) | 152 (0.65) | 145 (0.62) | 75 (0.84) | 71 (0.80) | 214 (1.08) | 226 (1.15) |
| Old myocardial infarction | 103 (0.72) | 100 (0.70) | 256 (0.81) | 231 (0.73) | 57 (0.57) | 59 (0.59) | 147 (0.63) | 160 (0.69) | 54 (0.61) | 63 (0.71) | 157 (0.80) | 156 (0.79) |
| Unstable angina | 128 (0.89) | 135 (0.94) | 295 (0.94) | 293 (0.93) | 71 (0.71) | 75 (0.75) | 150 (0.64) | 156 (0.67) | 69 (0.78) | 69 (0.78) | 175 (0.89) | 162 (0.82) |
| Stable angina | 168 (1.17) | 158 (1.10) | 401 (1.27) | 401 (1.27) | 93 (0.93) | 106 (1.06) | 236 (1.01) | 247 (1.06) | 96 (1.08) | 98 (1.10) | 240 (1.22) | 250 (1.27) |
| Other chronic ischemic heart disease | 220 (1.53) | 210 (1.46) | 608 (1.93) | 568 (1.80) | 112 (1.12) | 117 (1.17) | 318 (1.36) | 318 (1.36) | 131 (1.47) | 150 (1.69) | 378 (1.92) | 388 (1.97) |
| Coronary procedure (CABG or PTCA) | 265 (1.84) | 259 (1.80) | 603 (1.91) | 617 (1.96) | 153 (1.54) | 176 (1.77) | 351 (1.51) | 376 (1.61) | 181 (2.03) | 165 (1.85) | 407 (2.06) | 405 (2.05) |
| History of PTCA or CABG | 189 (1.31) | 215 (1.50) | 461 (1.46) | 471 (1.50) | 90 (0.90) | 90 (0.90) | 230 (0.99) | 237 (1.02) | 102 (1.15) | 99 (1.11) | 281 (1.42) | 279 (1.41) |
| Ischemic stroke | 164 (1.14) | 173 (1.20) | 451 (1.43) | 442 (1.40) | 99 (0.99) | 92 (0.92) | 272 (1.17) | 259 (1.11) | 95 (1.07) | 91 (1.02) | 274 (1.39) | 262 (1.33) |
| Congestive heart failure | 265 (1.84) | 268 (1.86) | 727 (2.31) | 741 (2.35) | 117 (1.17) | 124 (1.24) | 284 (1.22) | 289 (1.24) | 135 (1.52) | 146 (1.64) | 425 (2.15) | 449 (2.28) |
| Renal Dysfunction | 1362 (9.47) | 1363 (9.48) | 3723 (11.82) | 3719 (11.81) | 745 (7.48) | 719 (7.21) | 2305 (9.89) | 2239 (9.60) | 737 (8.29) | 730 (8.21) | 2088 (10.58) | 2071 (10.50) |
| Edema | 447 (3.11) | 445 (3.09) | 1064 (3.38) | 1059 (3.36) | 238 (2.39) | 236 (2.37) | 618 (2.65) | 608 (2.61) | 262 (2.95) | 251 (2.82) | 659 (3.34) | 628 (3.18) |
| Use of medications | ||||||||||||
| Past use of other antidiabetic agents | 4694 (32.64) | 4747 (33.01) | 9243 (29.35) | 9289 (29.50) | 2502 (25.11) | 2467 (24.75) | 5811 (24.92) | 5703 (24.46) | 2302 (25.88) | 2245 (25.24) | 4434 (22.47) | 4297 (21.78) |
| Past use of metformin | 2173 (15.11) | 2209 (15.36) | 4302 (13.66) | 4326 (13.74) | 1422 (14.27) | 1434 (14.39) | 3111 (13.34) | 3152 (13.52) | 1280 (14.39) | 1307 (14.69) | 2508 (12.71) | 2492 (12.63) |
| Past use of insulin | 486 (3.38) | 489 (3.40) | 1168 (3.71) | 1204 (3.82) | 329 (3.30) | 332 (3.33) | 827 (3.55) | 805 (3.45) | 300 (3.37) | 288 (3.24) | 768 (3.89) | 751 (3.81) |
| ACE inhibitor | 6029 (41.93) | 6037 (41.98) | 13323 (42.31) | 13376 (42.47) | 4163 (41.77) | 4199 (42.13) | 9865 (42.31) | 9903 (42.47) | 3276 (36.83) | 3245 (36.48) | 7483 (37.93) | 7521 (38.12) |
| ARBs | 3468 (24.12) | 3459 (24.06) | 7647 (24.28) | 7608 (24.16) | 2196 (22.03) | 2155 (21.62) | 5289 (22.68) | 5261 (22.56) | 2155 (24.23) | 2124 (23.88) | 4731 (23.98) | 4677 (23.70) |
| Beta blocker | 3546 (24.66) | 3579 (24.89) | 8194 (26.02) | 8197 (26.03) | 2269 (22.77) | 2255 (22.63) | 5548 (23.79) | 5564 (23.86) | 1982 (22.28) | 2001 (22.50) | 4695 (23.80) | 4608 (23.35) |
| Thiazides | 4218 (29.33) | 4124 (28.68) | 9077 (28.82) | 8971 (28.49) | 2775 (27.84) | 2803 (28.13) | 6579 (28.22) | 6592 (28.27) | 2460 (27.66) | 2415 (27.15) | 5382 (27.28) | 5281 (26.76) |
| Loop diuretics | 1066 (7.41) | 1058 (7.36) | 2450 (7.78) | 2423 (7.69) | 587 (5.89) | 594 (5.96) | 1394 (5.98) | 1372 (5.88) | 579 (6.51) | 557 (6.26) | 1382 (7.00) | 1340 (6.79) |
| Calcium channel blockers | 2938 (20.43) | 2880 (20.03) | 6587 (20.92) | 6495 (20.62) | 1952 (19.59) | 1929 (19.36) | 4615 (19.79) | 4660 (19.99) | 1674 (18.82) | 1662 (18.68) | 3762 (19.07) | 3726 (18.88) |
| Statins | 8002 (55.65) | 7982 (55.51) | 17915 (56.89) | 17811 (56.56) | 5286 (53.04) | 5278 (52.96) | 12849 (55.11) | 12909 (55.37) | 4592 (51.62) | 4573 (51.41) | 10478 (53.10) | 10481 (53.12) |
| Other lipid-lowering drugs | 2095 (14.57) | 2122 (14.76) | 4118 (13.08) | 4020 (12.77) | 1349 (13.54) | 1360 (13.65) | 2869 (12.30) | 2847 (12.21) | 1214 (13.65) | 1217 (13.68) | 2370 (12.01) | 2443 (12.38) |
| Oral anticoagulants | 396 (2.75) | 401 (2.79) | 4 (0.01) | 6 (0.02) | 219 (2.20) | 234 (2.35) | 4 (0.02) | 3 (0.01) | 214 (2.41) | 205 (2.30) | 4 (0.02) | 4 (0.02) |
| Antiplatelet | 785 (5.46) | 778 (5.41) | 1853 (5.88) | 1822 (5.79) | 475 (4.77) | 480 (4.82) | 1168 (5.01) | 1163 (4.99) | 450 (5.06) | 446 (5.01) | 1073 (5.44) | 1019 (5.16) |
| Health Care Utilization | ||||||||||||
| Any hospitalization | 808 (5.62) | 816 (5.67) | 1935 (6.14) | 1919 (6.09) | 475 (4.77) | 481 (4.83) | 1109 (4.76) | 1084 (4.65) | 486 (5.46) | 497 (5.59) | 1216 (6.16) | 1208 (6.12) |
| Any hospitalization within prior 30 days | 257 (1.79) | 266 (1.85) | 742 (2.36) | 750 (2.38) | 173 (1.74) | 174 (1.75) | 440 (1.89) | 416 (1.78) | 163 (1.83) | 176 (1.98) | 468 (2.37) | 466 (2.36) |
| N hospital days (mean, SD) | 0.29 (1.87) | 0.28 (1.90) | 0.32 (1.95) | 0.32 (2.15) | 0.22 (1.59) | 0.22 (1.45) | 0.23 (1.64) | 0.21 (1.44) | 0.28 (1.82) | 0.32 (2.61) | 0.33 (2.02) | 0.34 (2.44) |
| N physician visits (mean, SD) | 3.84 (2.91) | 3.78 (2.93) | 3.84 (3.00) | 3.80 (2.92) | 3.66 (2.83) | 3.56 (2.82) | 3.63 (2.85) | 3.53 (2.79) | 3.79 (2.89) | 3.68 (2.78) | 3.80 (3.00) | 3.72 (3.01) |
| N distinct non-insulin antidiabetic prescriptions (mean, SD) | 2.39 (0.88) | 2.40 (0.88) | 2.38 (0.88) | 2.37 (0.87) | 2.18 (0.77) | 2.19 (0.77) | 2.24 (0.80) | 2.24 (0.80) | 1.94 (0.65) | 1.95 (0.65) | 1.94 (0.66) | 1.94 (0.65) |
| N distinct prescriptions (mean, SD) | 8.46 (4.41) | 8.37 (4.32) | 8.58 (4.51) | 8.51 (4.44) | 8.02 (4.29) | 7.85 (4.10) | 8.17 (4.39) | 8.04 (4.18) | 7.88 (4.41) | 7.78 (4.19) | 8.01 (4.53) | 7.92 (4.30) |
| Number laboratory tests ordered (mean, SD) | 2.21 (2.07) | 2.16 (2.00) | 2.19 (2.05) | 2.17 (2.01) | 2.10 (1.93) | 2.06 (1.91) | 2.07 (1.90) | 2.04 (1.86) | 2.18 (2.10) | 2.14 (1.92) | 2.16 (2.04) | 2.16 (2.05) |
| Laboratory tests | ||||||||||||
| Patients with HbA1c available | 1359 (9.45) | 1420 (9.88) | 4239 (13.46) | 4497 (14.28) | 853 (8.56) | 879 (8.82) | 3021 (12.96) | 3064 (13.14) | 836 (9.40) | 972 (10.93) | 2683 (13.60) | 2755 (13.96) |
| HbA1c, % | 8.57 (2.06) | 8.62 (2.09) | 8.78 (7.39) | 8.85 (4.80) | 8.69 (2.02) | 8.78 (2.26) | 8.78 (6.49) | 8.88 (2.10) | 8.44 (2.17) | 8.88 (2.26) | 8.61 (6.44) | 9.07 (3.67) |
| Patients with creatinine available | 1464 (10.18) | 1468 (10.21) | 4581 (14.55) | 4718 (14.98) | 896 (8.99) | 874 (8.77) | 3236 (13.88) | 3168 (13.59) | 908 (10.21) | 953 (10.71) | 2903 (14.71) | 2855 (14.47) |
| Creatinine, mg/dL | 0.99 (0.32) | 0.96 (0.25) | 1.02 (0.34) | 0.98 (0.28) | 0.97 (0.30) | 0.96 (0.25) | 1.00 (0.31) | 0.98 (0.28) | 0.97 (0.31) | 0.94 (0.27) | 1.01 (0.33) | 0.96 (0.28) |
| eGFR, mL/min/1.73m2 | 100.93 (23.93) | 103.41 (20.84) | 96.29 (26.19) | 99.28 (23.24) | 102.62 (22.46) | 103.59 (21.67) | 97.36 (25.28) | 98.44 (23.62) | 102.59 (22.49) | 104.60 (21.48) | 97.98 (25.49) | 100.97 (22.86) |
| Patients with total cholesterol available | 1290 (8.97) | 1291 (8.98) | 4015 (12.75) | 4144 (13.16) | 791 (7.94) | 822 (8.25) | 2873 (12.32) | 2842 (12.19) | 806 (9.06) | 923 (10.38) | 2557 (12.96) | 2620 (13.28) |
| Total cholesterol, mg/dL | 181.44 (48.40) | 182.07 (51.12) | 182.20 (54.02) | 181.76 (50.41) | 184.39 (49.50) | 184.79 (54.86) | 183.26 (51.99) | 184.26 (50.50) | 184.16 (47.62) | 188.08 (54.59) | 184.60 (52.13) | 188.08 (56.11) |
| Patients with LDL available | 1183 (8.23) | 1193 (8.30) | 3711 (11.78) | 3824 (12.14) | 720 (7.22) | 766 (7.69) | 2636 (11.31) | 2656 (11.39) | 737 (8.29) | 855 (9.61) | 2350 (11.91) | 2419 (12.26) |
| LDL, mg/dL | 97.71 (37.84) | 98.87 (36.66) | 98.53 (38.67) | 98.40 (36.79) | 99.55 (38.17) | 99.27 (37.44) | 99.61 (38.74) | 99.34 (36.47) | 100.10 (37.86) | 102.88 (38.07) | 101.04 (38.46) | 102.02 (38.40) |
DPP-4i: dipeptidyl peptidase-4 inhibitors; SD: standard deviation; CABG: coronary artery bypass grafting; PTCA: percutaneous transluminal coronary angioplasty; ACE: Angiotensin-converting enzyme; ARBs: angiotensin II receptor blockers; HbA1c: hemoglobin A1c; eGFR: estimated glomerular filtration rate; LDL: low-density lipoprotein