Table-1: Population Characteristics.
Baseline clinical conditions were identified based on standardized definitions of clinical phenotypes corresponding to components of the Charlson Comorbidity Index. Socioeconomic status was assessed using the Area Deprivation Index (ADI), categorized into deciles (10-percentile intervals) according to established methodology46. Patient reported sex was used, and age was calculated on the index date. Baseline healthcare utilization included any type of clinical visit.
| Characteristics | UC-1 | UC-2 | UC-3 | UC-4 | UC-5 | |
|---|---|---|---|---|---|---|
| Dipeptidyl peptidase-4 inhibitors | ||||||
| New users, No. | 2820 | 2305 | 4741 | 3194 | 3623 | |
| Sex, No. | Female | 1356 (48.09%) | 1063 (46.12%) | 2217 (46.76%) | 1566 (49.03%) | 1772 (48.91%) |
| Male | 1464 (51.91%) | 1242 (53.88%) | 2524 (53.24%) | 1628 (50.97%) | 1851 (51.09%) | |
| Age, mean (SD) | 63.8 (12.8) | 65.3 (12.8) | 65.4 (13.1) | 65.9 (13.3) | 64.1 (12.6) | |
| Treatment Discontinuation, NO. | Yes | 1289 | 917 | 2068 | 1241 | 1580 |
| No | 1531 | 1388 | 2673 | 1953 | 2043 | |
| Baseline healthcare visits, mean (SD) | 39.8 (78.6) | 44.8 (77.9) | 52.2 (98.2) | 41.5 (78.2) | 47.8 (83.2) | |
| Area deprivation index, No. % | 1 | 13 (0.5%) | 492 (21.3%) | 1111 (23.4%) | 188 (5.9%) | 197 (5.4%) |
| 2 | 46 (1.6%) | 512 (22.2%) | 616 (13%) | 261 (8.2%) | 209 (5.8%) | |
| 3 | 113 (4%) | 205 (8.9%) | 684 (14.4%) | 479 (15%) | 253 (7%) | |
| 4 | 165 (5.9%) | 168 (7.3%) | 494 (10.4%) | 400 (12.5%) | 483 (13.3%) | |
| 5 | 178 (6.3%) | 106 (4.6%) | 509 (10.7%) | 557 (17.4%) | 412 (11.4%) | |
| 6 | 250 (8.9%) | 127 (5.5%) | 409 (8.6%) | 540 (16.9%) | 408 (11.3%) | |
| 7 | 377 (13.4%) | 107 (4.6%) | 303 (6.4%) | 304 (9.5%) | 504 (13.9%) | |
| 8 | 498 (17.7%) | 157 (6.8%) | 177 (3.7%) | 168 (5.3%) | 365 (10.1%) | |
| 9 | 664 (23.5%) | 163 (7.1%) | 124 (2.6%) | 106 (3.3%) | 216 (6%) | |
| 10 | 403 (14.3%) | 188 (8.2%) | 142 (3%) | 120 (3.8%) | 401 (11.1%) | |
| NA | 113 (4%) | 80 (3.5%) | 172 (3.6%) | 71 (2.2%) | 175 (4.8%) | |
| Baseline comorbidities, No. % | Myocardial infarction | 196 (7%) | 158 (6.9%) | 237 (5%) | 193 (6%) | 297 (8.2%) |
| Congestive heart failure | 332 (11.8%) | 349 (15.1%) | 450 (9.5%) | 362 (11.3%) | 647 (17.9%) | |
| Cerebrovascular disease | 238 (8.4%) | 234 (10.2%) | 321 (6.8%) | 295 (9.2%) | 276 (7.6%) | |
| Dementia | 85 (3%) | 95 (4.1%) | 136 (2.9%) | 147 (4.6%) | 126 (3.5%) | |
| Chronic pulmonary disease | 412 (14.6%) | 398 (17.3%) | 574 (12.1%) | 305 (9.5%) | 581 (16%) | |
| Rheumatologic disease | 67 (2.4%) | 75 (3.3%) | 138 (2.9%) | 81 (2.5%) | 97 (2.7%) | |
| Peptic ulcer disease | 78 (2.8%) | 67 (2.9%) | 142 (3%) | 70 (2.2%) | 158 (4.4%) | |
| Mild liver disease | 214 (7.6%) | 272 (11.8%) | 437 (9.2%) | 214 (6.7%) | 560 (15.5%) | |
| Hemoplegia or paralegia | 62 (2.2%) | 61 (2.6%) | 51 (1.1%) | 71 (2.2%) | 51 (1.4%) | |
| Renal disease | 789 (28%) | 846 (36.7%) | 1202 (25.4%) | 948 (29.7%) | 1368 (37.8%) | |
| AIDS/HIV | 12 (0.4%) | 45 (2%) | 21 (0.4%) | 25 (0.8%) | 58 (1.6%) | |
| Metastatic solid tumor | Less than 10 | Less than 10 | Less than 10 | Less than 10 | Less than 10 | |
| Moderate to severe liver disease | 56 (2%) | 114 (4.9%) | 181 (3.8%) | 62 (1.9%) | 323 (8.9%) | |
| Any malignancy | 423 (15%) | 527 (22.9%) | 905 (19.1%) | 552 (17.3%) | 689 (19%) | |
| GLP-1 receptor agonists | ||||||
| New users, No. | 3669 | 3682 | 6802 | 2807 | 5893 | |
| Sex, No. | Female | 2274 (61.98%) | 2125 (57.71%) | 3985 (58.59%) | 1706 (60.78%) | 3309 (56.15%) |
| Male | 1395 (38.02%) | 1557 (42.29%) | 2817 (41.41%) | 1101 (39.22%) | 2584 (43.85%) | |
| Age, mean (SD) | 57.5 (12.9) | 58.1 (14.1) | 56.9 (13.7) | 57.1 (14.2) | 59.1 (12.9) | |
| Treatment Discontinuation, NO. | Yes | 639 | 595 | 1072 | 596 | 1097 |
| No | 3030 | 3087 | 5730 | 2211 | 4796 | |
| Baseline healthcare visits, mean (SD) | 96.8 (123.4) | 75.5 (114.5) | 92.7 (130.8) | 66.4 (103.2) | 92.2 (140.8) | |
| Area deprivation index, No. % | 1 | 11 (0.3%) | 1047 (28.4%) | 1531 (22.5%) | 251 (8.9%) | 484 (8.2%) |
| 2 | 66 (1.8%) | 795 (21.6%) | 977 (14.4%) | 323 (11.5%) | 412 (7%) | |
| 3 | 184 (5%) | 379 (10.3%) | 1043 (15.3%) | 466 (16.6%) | 461 (7.8%) | |
| 4 | 303 (8.3%) | 295 (8%) | 846 (12.4%) | 352 (12.5%) | 897 (15.2%) | |
| 5 | 312 (8.5%) | 174 (4.7%) | 770 (11.3%) | 395 (14.1%) | 658 (11.2%) | |
| 6 | 422 (11.5%) | 148 (4%) | 556 (8.2%) | 433 (15.4%) | 678 (11.5%) | |
| 7 | 486 (13.2%) | 169 (4.6%) | 364 (5.4%) | 199 (7.1%) | 793 (13.5%) | |
| 8 | 687 (18.7%) | 183 (5%) | 247 (3.6%) | 139 (5%) | 531 (9%) | |
| 9 | 679 (18.5%) | 192 (5.2%) | 140 (2.1%) | 92 (3.3%) | 341 (5.8%) | |
| 10 | 405 (11%) | 186 (5.1%) | 121 (1.8%) | 98 (3.5%) | 415 (7%) | |
| NA | 114 (3.1%) | 114 (3.1%) | 207 (3%) | 59 (2.1%) | 223 (3.8%) | |
| Baseline comorbidities, No. % | Myocardial infarction | 200 (5.5%) | 152 (4.1%) | 229 (3.4%) | 108 (3.8%) | 422 (7.2%) |
| Congestive heart failure | 343 (9.3%) | 324 (8.8%) | 376 (5.5%) | 188 (6.7%) | 760 (12.9%) | |
| Cerebrovascular disease | 273 (7.4%) | 212 (5.8%) | 357 (5.2%) | 160 (5.7%) | 422 (7.2%) | |
| Dementia | 26 (0.7%) | 36 (1%) | 42 (0.6%) | 30 (1.1%) | 88 (1.5%) | |
| Chronic pulmonary disease | 735 (20%) | 547 (14.9%) | 1209 (17.8%) | 376 (13.4%) | 1167 (19.8%) | |
| Rheumatologic disease | 150 (4.1%) | 125 (3.4%) | 337 (5%) | 119 (4.2%) | 252 (4.3%) | |
| Peptic ulcer disease | 154 (4.2%) | 102 (2.8%) | 268 (3.9%) | 87 (3.1%) | 303 (5.1%) | |
| Mild liver disease | 501 (13.7%) | 566 (15.4%) | 787 (11.6%) | 306 (10.9%) | 1011 (17.2%) | |
| Hemoplegia or paralegia | 54 (1.5%) | 28 (0.8%) | 35 (0.5%) | 36 (1.3%) | 78 (1.3%) | |
| Renal disease | 669 (18.2%) | 840 (22.8%) | 950 (14%) | 483 (17.2%) | 1302 (22.1%) | |
| AIDS/HIV | 27 (0.7%) | 104 (2.8%) | 67 (1%) | 30 (1.1%) | 304 (5.2%) | |
| Metastatic solid tumor | Less than 10 | Less than 10 | Less than 10 | Less than 10 | Less than 10 | |
| Moderate to severe liver disease | 40 (1.1%) | 126 (3.4%) | 97 (1.4%) | 25 (0.9%) | 171 (2.9%) | |
| Any malignancy | 546 (14.9%) | 768 (20.9%) | 1134 (16.7%) | 478 (17%) | 1117 (19%) | |
| Sodium-glucose cotransporter-2 inhibitors | ||||||
| New users, No. | 3349 | 3293 | 5505 | 3057 | 4038 | |
| Sex, No. | Female | 1357 (40.52%) | 1249 (37.93%) | 2096 (38.07%) | 1210 (39.58%) | 1562 (38.68%) |
| Male | 1992 (59.48%) | 2044 (62.07%) | 3409 (61.93%) | 1847 (60.42%) | 2476 (61.32%) | |
| Age, mean (SD) | 64.6 (13.7) | 66.4 (14.3) | 64.7 (14.2) | 63.8 (14.2) | 66.1 (13) | |
| Treatment Discontinuation, NO. | Yes | 774 | 751 | 1484 | 821 | 1164 |
| No | 2575 | 2542 | 4021 | 2236 | 2874 | |
| Baseline healthcare visits, mean (SD) | 109.9 (161.9) | 80.9 (121.3) | 95 (154.5) | 62.8 (127.3) | 100.4 (164.8) | |
| Area deprivation index, No. % | 1 | 11 (0.3%) | 914 (27.8%) | 1273 (23.1%) | 193 (6.3%) | 378 (9.4%) |
| 2 | 51 (1.5%) | 809 (24.6%) | 743 (13.5%) | 245 (8%) | 299 (7.4%) | |
| 3 | 154 (4.6%) | 309 (9.4%) | 819 (14.9%) | 479 (15.7%) | 319 (7.9%) | |
| 4 | 209 (6.2%) | 255 (7.7%) | 643 (11.7%) | 396 (13%) | 611 (15.1%) | |
| 5 | 237 (7.1%) | 135 (4.1%) | 559 (10.2%) | 509 (16.7%) | 408 (10.1%) | |
| 6 | 331 (9.9%) | 130 (3.9%) | 468 (8.5%) | 512 (16.7%) | 484 (12%) | |
| 7 | 385 (11.5%) | 152 (4.6%) | 300 (5.4%) | 323 (10.6%) | 501 (12.4%) | |
| 8 | 576 (17.2%) | 179 (5.4%) | 225 (4.1%) | 164 (5.4%) | 338 (8.4%) | |
| 9 | 798 (23.8%) | 181 (5.5%) | 141 (2.6%) | 70 (2.3%) | 240 (5.9%) | |
| 10 | 496 (14.8%) | 146 (4.4%) | 129 (2.3%) | 110 (3.6%) | 300 (7.4%) | |
| NA | 101 (3%) | 83 (2.5%) | 205 (3.7%) | 56 (1.8%) | 160 (4%) | |
| Baseline comorbidities, No. % | Myocardial infarction | 785 (23.4%) | 550 (16.7%) | 704 (12.8%) | 415 (13.6%) | 634 (15.7%) |
| Congestive heart failure | 1469 (43.9%) | 1256 (38.1%) | 1479 (26.9%) | 803 (26.3%) | 1465 (36.3%) | |
| Cerebrovascular disease | 475 (14.2%) | 441 (13.4%) | 546 (9.9%) | 316 (10.3%) | 500 (12.4%) | |
| Dementia | 71 (2.1%) | 98 (3%) | 104 (1.9%) | 80 (2.6%) | 98 (2.4%) | |
| Chronic pulmonary disease | 1044 (31.2%) | 629 (19.1%) | 894 (16.2%) | 421 (13.8%) | 925 (22.9%) | |
| Rheumatologic disease | 154 (4.6%) | 126 (3.8%) | 215 (3.9%) | 85 (2.8%) | 168 (4.2%) | |
| Peptic ulcer disease | 198 (5.9%) | 131 (4%) | 221 (4%) | 108 (3.5%) | 230 (5.7%) | |
| Mild liver disease | 393 (11.7%) | 498 (15.1%) | 523 (9.5%) | 314 (10.3%) | 498 (12.3%) | |
| Hemoplegia or paralegia | 79 (2.4%) | 64 (1.9%) | 57 (1%) | 79 (2.6%) | 67 (1.7%) | |
| Renal disease | 1402 (41.9%) | 1555 (47.2%) | 1786 (32.4%) | 909 (29.7%) | 1599 (39.6%) | |
| AIDS/HIV | 31 (0.9%) | 59 (1.8%) | 42 (0.8%) | 26 (0.9%) | 89 (2.2%) | |
| Metastatic solid tumor | Less than 10 | Less than 10 | Less than 10 | Less than 10 | Less than 10 | |
| Moderate to severe liver disease | 116 (3.5%) | 168 (5.1%) | 147 (2.7%) | 87 (2.8%) | 146 (3.6%) | |
| Any malignancy | 710 (21.2%) | 871 (26.5%) | 1223 (22.2%) | 540 (17.7%) | 1010 (25%) | |
| Sulfonylureas | ||||||
| New users, No. | 6756 | 4383 | 5992 | 6033 | 4848 | |
| Sex, No. | Female | 2934 (43.43%) | 1901 (43.37%) | 2569 (42.87%) | 2863 (47.46%) | 2116 (43.65%) |
| Male | 3822 (56.57%) | 2482 (56.63%) | 3423 (57.13%) | 3170 (52.54%) | 2732 (56.35%) | |
| Age, mean (SD) | 61.3 (12.4) | 62 (12.4) | 62.7 (13) | 60.5 (13.5) | 61.4 (12.4) | |
| Treatment Discontinuation, NO. | Yes | 2701 | 1769 | 2504 | 2174 | 2204 |
| No | 4055 | 2614 | 3488 | 3859 | 2644 | |
| Baseline healthcare visits, mean (SD) | 27.3 (49.1) | 28.1 (49.5) | 32.9 (58.9) | 21 (40.9) | 27.3 (57.8) | |
| Area deprivation index, No. % | 1 | 43 (0.6%) | 861 (19.6%) | 1097 (18.3%) | 158 (2.6%) | 183 (3.8%) |
| 2 | 143 (2.1%) | 1050 (24%) | 684 (11.4%) | 257 (4.3%) | 221 (4.6%) | |
| 3 | 244 (3.6%) | 443 (10.1%) | 795 (13.3%) | 663 (11%) | 269 (5.5%) | |
| 4 | 415 (6.1%) | 401 (9.1%) | 681 (11.4%) | 787 (13%) | 702 (14.5%) | |
| 5 | 485 (7.2%) | 215 (4.9%) | 716 (11.9%) | 1042 (17.3%) | 560 (11.6%) | |
| 6 | 606 (9%) | 221 (5%) | 618 (10.3%) | 1409 (23.4%) | 599 (12.4%) | |
| 7 | 868 (12.8%) | 238 (5.4%) | 417 (7%) | 725 (12%) | 772 (15.9%) | |
| 8 | 1134 (16.8%) | 270 (6.2%) | 344 (5.7%) | 425 (7%) | 599 (12.4%) | |
| 9 | 1567 (23.2%) | 301 (6.9%) | 214 (3.6%) | 183 (3%) | 269 (5.5%) | |
| 10 | 981 (14.5%) | 245 (5.6%) | 179 (3%) | 266 (4.4%) | 413 (8.5%) | |
| NA | 270 (4%) | 138 (3.1%) | 247 (4.1%) | 118 (2%) | 261 (5.4%) | |
| Baseline comorbidities, No. % | Myocardial infarction | 361 (5.3%) | 226 (5.2%) | 309 (5.2%) | 337 (5.6%) | 286 (5.9%) |
| Congestive heart failure | 626 (9.3%) | 459 (10.5%) | 451 (7.5%) | 497 (8.2%) | 548 (11.3%) | |
| Cerebrovascular disease | 471 (7%) | 253 (5.8%) | 289 (4.8%) | 392 (6.5%) | 246 (5.1%) | |
| Dementia | 136 (2%) | 98 (2.2%) | 130 (2.2%) | 162 (2.7%) | 113 (2.3%) | |
| Chronic pulmonary disease | 745 (11%) | 389 (8.9%) | 526 (8.8%) | 379 (6.3%) | 475 (9.8%) | |
| Rheumatologic disease | 130 (1.9%) | 85 (1.9%) | 124 (2.1%) | 96 (1.6%) | 103 (2.1%) | |
| Peptic ulcer disease | 130 (1.9%) | 86 (2%) | 124 (2.1%) | 95 (1.6%) | 135 (2.8%) | |
| Mild liver disease | 436 (6.5%) | 599 (13.7%) | 468 (7.8%) | 337 (5.6%) | 440 (9.1%) | |
| Hemoplegia or paralegia | 103 (1.5%) | 83 (1.9%) | 56 (0.9%) | 126 (2.1%) | 63 (1.3%) | |
| Renal disease | 1502 (22.2%) | 1401 (32%) | 1446 (24.1%) | 1070 (17.7%) | 1007 (20.8%) | |
| AIDS/HIV | 21 (0.3%) | 68 (1.6%) | 33 (0.6%) | 44 (0.7%) | 131 (2.7%) | |
| Metastatic solid tumor | Less than 10 | Less than 10 | Less than 10 | Less than 10 | Less than 10 | |
| Moderate to severe liver disease | 64 (0.9%) | 281 (6.4%) | 116 (1.9%) | 87 (1.4%) | 169 (3.5%) | |
| Any malignancy | 767 (11.4%) | 917 (20.9%) | 907 (15.1%) | 689 (11.4%) | 727 (15%) |