TABLE 1.
Baseline and clinical characteristics of patients with SGLT2I versus DPP4I use before and after propensity score matching (1:1).
| Before matching | After matching | |||||||
|---|---|---|---|---|---|---|---|---|
| Characteristics | All (N = 60,112) Mean (SD); N or count (%) | SGLT2I users (N = 18,167) Mean (SD); N or count (%) | DPP4I users (N = 41,945) Mean (SD); N or count (%) | SMD | All (N = 36,334) Mean (SD); N or count (%) | SGLT2I users (N = 18,167) Mean (SD); N or count (%) | DPP4I users (N = 18,167) Mean (SD); N or count (%) | SMD |
| Demographics | ||||||||
| Male gender | 33,883 (56.36%) | 11,138 (61.30%) | 22,745 (54.22%) | 0.14 | 22,288 (61.34%) | 11,147 (61.35%) | 11,141 (61.32%) | <0.01 |
| Female gender | 26,229 (43.63%) | 7029 (38.69%) | 19,200 (45.77%) | 0.14 | 14,046 (38.65%) | 7020 (38.64%) | 7026 (38.67%) | <0.01 |
| Baseline age, years | 62.1 (12.4); n = 60,112 | 57.8 (11.2); n = 18,167 | 63.9 (12.5); n = 41,945 | 0.51 a | 58.2 (11.0); n = 36,334 | 57.8 (11.2); n = 18,167 | 58.7 (10.9); n = 18,167 | 0.08 |
| 18–50 | 9057 (15.06%) | 3878 (21.34%) | 5179 (12.34%) | 0.24 a | 7212 (19.84%) | 3888 (21.40%) | 3324 (18.29%) | 0.08 |
| 50–60 | 17,550 (29.19%) | 6524 (35.91%) | 11,026 (26.28%) | 0.21 a | 13,285 (36.56%) | 6543 (36.01%) | 6742 (37.11%) | 0.02 |
| 60–70 | 18,029 (29.99%) | 5464 (30.07%) | 12,565 (29.95%) | <0.01 | 11,194 (30.80%) | 5457 (30.03%) | 5737 (31.57%) | 0.03 |
| 70–80 | 10,338 (17.19%) | 1883 (10.36%) | 8455 (20.15%) | 0.27 a | 3766 (10.36%) | 1870 (10.29%) | 1896 (10.43%) | <0.01 |
| >80 | 5145 (8.55%) | 421 (2.31%) | 4724 (11.26%) | 0.36 a | 881 (2.42%) | 412 (2.26%) | 469 (2.58%) | 0.02 |
| Past comorbidities | ||||||||
| Charlson standard comorbidity index | 1.9 (1.4); n = 60,112 | 1.5 (1.2); n = 18,167 | 2.1 (1.4); n = 41,945 | 0.45 a | 1.5 (1.2); n = 36,334 | 1.52 (1.17); n = 18,167 | 1.55 (1.14); n = 18,167 | 0.02 |
| Duration from earliest diabetes mellitus date to baseline date, day | 619.9 (1341.9); n = 60,112 | 616.9 (1352.3); n = 18,167 | 621.2 (1337.4); n = 41,945 | <0.01 | 590.9 (1323.1); n = 36,334 | 618.7 (1354.2); n = 18,167 | 563.1 (1290.6); n = 18,167 | 0.04 |
| Hypertension | 13,376 (22.25%) | 4284 (23.58%) | 9092 (21.67%) | 0.05 | 8325 (22.91%) | 4283 (23.57%) | 4042 (22.24%) | 0.03 |
| Hyperlipidaemia | 1620 (2.69%) | 66 2 (3.64%) | 958 (2.28%) | 0.08 | 1265 (3.48%) | 659 (3.62%) | 606 (3.33%) | 0.02 |
| Hypotension | 350 (0.58%) | 76 (0.41%) | 274 (0.65%) | 0.03 | 152 (0.41%) | 75 (0.41%) | 77 (0.42%) | <0.01 |
| Overweight, obesity and hyperalimentation | 432 (0.71%) | 297 (1.63%) | 135 (0.32%) | 0.13 | 576 (1.58%) | 300 (1.65%) | 276 (1.51%) | 0.01 |
| Gout | 1510 (2.51%) | 394 (2.16%) | 1116 (2.66%) | 0.03 | 782 (2.15%) | 394 (2.16%) | 388 (2.13%) | <0.01 |
| Heart failure | 1629 (2.70%) | 447 (2.46%) | 1182 (2.81%) | 0.02 | 874 (2.40%) | 447 (2.46%) | 427 (2.35%) | 0.01 |
| Acute myocardial infarction | 1521 (2.53%) | 616 (3.39%) | 905 (2.15%) | 0.08 | 1210 (3.33%) | 613 (3.37%) | 597 (3.28%) | <0.01 |
| Ischaemic heart disease | 5680 (9.44%) | 2342 (12.89%) | 3338 (7.95%) | 0.16 | 4466 (12.29%) | 2333 (12.84%) | 2133 (11.74%) | 0.03 |
| Peripheral vascular disease | 375 (0.62%) | 97 (0.53%) | 278 (0.66%) | 0.02 | 194 (0.53%) | 99 (0.54%) | 95 (0.52%) | <0.01 |
| Stroke/transient ischaemic attack | 1777 (2.95%) | 474 (2.60%) | 1303 (3.10%) | 0.03 | 940 (2.58%) | 477 (2.62%) | 463 (2.54%) | <0.01 |
| Atrial fibrillation | 1325 (2.20%) | 388 (2.13%) | 937 (2.23%) | 0.01 | 766 (2.10%) | 386 (2.12%) | 380 (2.09%) | <0.01 |
| Diabetic eye disease | 4045 (6.72%) | 1322 (7.27%) | 2723 (6.49%) | 0.03 | 2459 (6.76%) | 1321 (7.27%) | 1138 (6.26%) | 0.04 |
| Alcohol dependence | 119 (0.19%) | 22 (0.12%) | 97 (0.23%) | 0.03 | 44 (0.12%) | 23 (0.12%) | 21 (0.11%) | <0.01 |
| Chronic liver disease and cirrhosis | 1195 (1.98%) | 513 (2.82%) | 682 (1.62%) | 0.08 | 995 (2.73%) | 515 (2.83%) | 480 (2.64%) | 0.01 |
| Viral hepatitis | 629 (1.04%) | 209 (1.15%) | 420 (1.00%) | 0.01 | 414 (1.13%) | 211 (1.16%) | 203 (1.11%) | <0.01 |
| History of acute liver injury | 159 (0.26%) | 36 (0.19%) | 123 (0.29%) | 0.02 | 72 (0.19%) | 36 (0.19%) | 36 (0.19%) | <0.01 |
| Other liver disease | 612 (1.01%) | 163 (0.89%) | 449 (1.07%) | 0.02 | 324 (0.89%) | 160 (0.88%) | 164 (0.90%) | <0.01 |
| Autoimmune disease tissue | 620 (1.03%) | 198 (1.08%) | 422 (1.00%) | 0.01 | 386 (1.06%) | 200 (1.10%) | 186 (1.02%) | 0.01 |
| Infections by pathogens associated with cancer development (Helicobacterpylori, Human papillomavirus, Infectious mononucleosis) | 13 (0.02%) | 6 (0.03%) | 7 (0.01%) | 0.01 | 12 (0.03%) | 6 (0.03%) | 6 (0.03%) | <0.01 |
| Chronic obstructive pulmonary disease | 69 (0.11%) | 12 (0.06%) | 57 (0.13%) | 0.02 | 24 (0.06%) | 12 (0.06%) | 12 (0.06%) | <0.01 |
| Gastrointestinal disease | 1353 (2.25%) | 349 (1.92%) | 1004 (2.39%) | 0.03 | 690 (1.89%) | 350 (1.92%) | 340 (1.87%) | <0.01 |
| Medications | ||||||||
| SGLT2I vs. DPP4I | 18,167 (30.22%) | 18,167 (100.00%) | 0 (0.00%) | inf a | 18,167 (50.00%) | 18,167 (100.00%) | 0 (0.00%) | inf a |
| SGLT2I frequency | 7.4 (10.1); n = 18,167 | 7.4 (10.1); n = 18,167 | – | – | 7.3 (10.0); n = 18,167 | 7.3 (10.0); n = 18,167 | – | – |
| DPP4I frequency | 5.5 (7.2); n = 41,945 | – | 5.5 (7.2); n = 41,945 | – | 6.3 (8.0); n = 18,167 | – | 6.3 (8.0); n = 18,167 | – |
| SGLT2I duration, days | 538.1 (674.5); n = 18,167 | 538.1 (674.5); n = 18,167 | – | – | 538.5 (673.6); n = 18,167 | 538.5 (673.6); n = 18,167 | – | – |
| DPP4I duration, days | 528.9 (301.0); n = 41,945 | – | 528.9 (301.0); n = 41,945 | – | 575.3 (360.3); n = 18,167 | – | 575.3 (360.3); n = 18,167 | – |
| Metformin | 54,407 (90.50%) | 16,917 (93.11%) | 37,490 (89.37%) | 0.13 | 33,945 (93.42%) | 16,923 (93.15%) | 17,022 (93.69%) | 0.02 |
| Sulphonylurea | 46,521 (77.39%) | 12,899 (71.00%) | 33,622 (80.15%) | 0.21 a | 26,376 (72.59%) | 12,889 (70.94%) | 13,487 (74.23%) | 0.07 |
| Insulin | 29,349 (48.82%) | 9517 (52.38%) | 19,832 (47.28%) | 0.1 | 19,074 (52.49%) | 9509 (52.34%) | 9565 (52.65%) | 0.01 |
| Acarbose | 1566 (2.60%) | 751 (4.13%) | 815 (1.94%) | 0.13 | 1429 (3.93%) | 744 (4.09%) | 685 (3.77%) | 0.02 |
| Thiazolidinedone | 12,046 (20.03%) | 5130 (28.23%) | 6916 (16.48%) | 0.28 a | 9569 (26.33%) | 5134 (28.26%) | 4435 (24.41%) | 0.09 |
| Glucagon‐like peptide‐1 receptor agonists | 2044 (3.40%) | 1505 (8.28%) | 539 (1.28%) | 0.33 a | 2797 (7.69%) | 1506 (8.28%) | 1291 (7.10%) | 0.04 |
| ACEI/ARB | 18,249 (30.35%) | 11,149 (61.36%) | 7100 (16.92%) | 1.02 a | 22,352 (61.51%) | 11,152 (61.38%) | 11,200 (61.65%) | 0.01 |
| Antidepressants | 2742 (4.56%) | 1665 (9.16%) | 1077 (2.56%) | 0.28 a | 2971 (8.17%) | 1661 (9.14%) | 1310 (7.21%) | 0.07 |
| Antihypertensive drugs | 2311 (3.84%) | 1681 (9.25%) | 630 (1.50%) | 0.35 a | 3051 (8.39%) | 1680 (9.24%) | 1371 (7.54%) | 0.06 |
| Antihepatitis | 809 (1.34%) | 336 (1.84%) | 473 (1.12%) | 0.06 | 664 (1.82%) | 337 (1.85%) | 327 (1.79%) | <0.01 |
| Anticoagulants | 29,401 (48.91%) | 18,166 (99.99%) | 11,235 (26.78%) | 2.34 a | 36,332 (99.99%) | 18,166 (99.99%) | 18,166 (99.99%) | <0.01 |
| Antiplatelets | 10,115 (16.82%) | 5981 (32.92%) | 4134 (9.85%) | 0.59 a | 11,686 (32.16%) | 5975 (32.88%) | 5711 (31.43%) | 0.03 |
| Statins and fibrates | 34,307 (57.07%) | 13,773 (75.81%) | 20,534 (48.95%) | 0.58 a | 27,749 (76.37%) | 13,780 (75.85%) | 13,969 (76.89%) | 0.02 |
| Nitrates | 4652 (7.73%) | 2688 (14.79%) | 1964 (4.68%) | 0.35 a | 5278 (14.52%) | 2684 (14.77%) | 2594 (14.27%) | 0.01 |
| Non‐steroidal anti‐inflammatory drugs | 9719 (16.16%) | 5734 (31.56%) | 3985 (9.50%) | 0.57 a | 11,369 (31.29%) | 5730 (31.54%) | 5639 (31.03%) | 0.01 |
| Diuretics | 10,179 (16.93%) | 5633 (31.00%) | 4546 (10.83%) | 0.51 a | 11,095 (30.53%) | 5628 (30.97%) | 5467 (30.09%) | 0.02 |
| Beta‐blockers | 8075 (13.43%) | 4696 (25.84%) | 3379 (8.05%) | 0.49 a | 9261 (25.48%) | 4694 (25.83%) | 4567 (25.13%) | 0.02 |
| Calcium channel blockers | 14,154 (23.54%) | 8107 (44.62%) | 6047 (14.41%) | 0.70 a | 16,462 (45.30%) | 8102 (44.59%) | 8360 (46.01%) | 0.03 |
| Subclinical biomarkers | ||||||||
| Abbreviated MDRD, mL/min/1.73 m2 | 81.4 (27.9); n = 49,633 | 90.1 (23.8); n = 15,520 | 77.4 (28.8); n = 34,113 | 0.48 a | 88.6 (23.5); n = 29,687 | 90.1 (23.8); n = 15,514 | 86.9 (23.1); n = 14,173 | 0.14 |
| Most severe renal damage (<15 mL/min/1.73 m2) | 436.0 (0.72%) | 16.0 (0.08%) | 420.0 (1.00%) | 0.12 | 40.0 (0.11%) | 16.0 (0.08%) | 24.0 (0.13%) | 0.01 |
| Severe renal damage ([15, 30] mL/min/1.73 m2) | 1108.0 (1.84%) | 41.0 (0.22%) | 1067.0 (2.54%) | 0.2 | 111.0 (0.30%) | 39.0 (0.21%) | 72.0 (0.39%) | 0.03 |
| Moderate to severe renal damage ([30, 45] mL/min/1.73 m2) | 3548.0 (5.90%) | 265.0 (1.45%) | 3283.0 (7.82%) | 0.31 a | 657.0 (1.80%) | 261.0 (1.43%) | 396.0 (2.17%) | 0.06 |
| Mild to moderate renal damage ([45, 60] mL/min/1.73 m2) | 5816.0 (9.67%) | 999.0 (5.49%) | 4817.0 (11.48%) | 0.22 a | 2222.0 (6.11%) | 1000.0 (5.50%) | 1222.0 (6.72%) | 0.05 |
| Mild renal damage ([60, 90] mL/min/1.73 m2) | 19920.0 (33.13%) | 6788.0 (37.36%) | 13132.0 (31.30%) | 0.13 | 12997.0 (35.77%) | 6783.0 (37.33%) | 6214.0 (34.20%) | 0.07 |
| Chronic kidney disease (>90 mL/min/1.73 m2) | 18805.0 (31.28%) | 7411.0 (40.79%) | 11394.0 (27.16%) | 0.29 a | 13660.0 (37.59%) | 7415.0 (40.81%) | 6245.0 (34.37%) | 0.13 |
| Neutrophil‐to‐lymphocyte ratio | 3.4 (4.5); n = 23,978 | 3.0 (3.9); n = 8133 | 3.6 (4.8); n = 15,845 | 0.15 | 3.1 (3.8); n = 15,970 | 3.0 (3.9); n = 8146 | 3.2 (3.7); n = 7824 | 0.05 |
| Platelet‐to‐lymphocyte ratio | 142.0 (148.2); n = 23,976 | 133.5 (168.7); n = 8131 | 146.4 (136.3); n = 15,845 | 0.08 | 133.6 (137.8); n = 15,969 | 133.3 (168.5); n = 8144 | 133.9 (95.8); n = 7825 | <0.01 |
| Neutrophil‐to‐high‐density lipoprotein ratio | 0.3 (0.2); n = 21,968 | 0.27 (0.16); n = 7755 | 0.27 (0.2); n = 14,213 | 0.01 | 0.3 (0.2); n = 15,080 | 0.27 (0.16); n = 7770 | 0.27 (0.16); n = 7310 | 0.01 |
| Low density lipoprotein ratio‐to‐high density lipoprotein ratio | 2.1 (0.9); n = 46,116 | 2.14 (0.83); n = 14,654 | 2.1 (0.86); n = 31,462 | 0.05 | 2.1 (0.8); n = 27,933 | 2.14 (0.83); n = 14,653 | 2.13 (0.84); n = 13,280 | 0.01 |
| Triglyceride‐glucose index | 7.6 (0.7); n = 42,025 | 7.6 (0.7); n = 13,571 | 7.5 (0.7); n = 28,454 | 0.15 | 7.6 (0.7); n = 25,514 | 7.64 (0.72); n = 13,576 | 7.64 (0.73); n = 11,938 | 0.01 |
| Protein‐to‐creatinine ratio | 3.0 (1.5); n = 29,872 | 3.4 (1.5); n = 10,496 | 2.8 (1.5); n = 19,376 | 0.34 a | 3.3 (1.5); n = 19,746 | 3.4 (1.5); n = 10,502 | 3.2 (1.4); n = 9244 | 0.13 |
| Aspartate aminotransferase‐to‐alanine transaminase ratio | 1.1 (3.2); n = 8773 | 0.9 (1.0); n = 3284 | 1.2 (3.9); n = 5489 | 0.08 | 0.9 (0.8); n = 6377 | 0.92 (0.99); n = 3279 | 0.94 (0.5); n = 3098 | 0.03 |
| Complete blood counts, renal and liver functions | ||||||||
| Mean corpuscular volume, fL | 87.1 (7.5); n = 29,998 | 86.6 (7.2); n = 10,523 | 87.4 (7.6); n = 19,475 | 0.1 | 86.7 (7.2); n = 19,809 | 86.6 (7.2); n = 10,529 | 86.8 (7.3); n = 9280 | 0.03 |
| Potassium, mmol/L | 4.3 (0.5); n = 49,471 | 4.3 (0.4); n = 15,489 | 4.4 (0.5); n = 33,982 | 0.1 | 4.3 (0.4); n = 29,604 | 4.31 (0.43); n = 15,483 | 4.27 (0.45); n = 14,121 | 0.1 |
| Albumin, g/L | 41.9 (3.8); n = 37,720 | 42.5 (3.3); n = 13,085 | 41.5 (4.0); n = 24,635 | 0.27 a | 42.5 (3.3); n = 24,595 | 42.5 (3.3); n = 13,089 | 42.4 (3.4); n = 11,506 | 0.03 |
| Sodium, mmol/L | 139.3 (2.9); n = 49,494 | 139.1 (2.7); n = 15,492 | 139.3 (3.0); n = 34,002 | 0.07 | 139.3 (2.7); n = 29,612 | 139.1 (2.7); n = 15,486 | 139.4 (2.7); n = 14,126 | 0.08 |
| Urea, mmol/L | 6.4 (3.3); n = 49,483 | 5.7 (2.0); n = 15,486 | 6.8 (3.7); n = 33,997 | 0.34 a | 5.8 (2.1); n = 29,607 | 5.7 (2.0); n = 15,480 | 5.8 (2.2); n = 14,127 | 0.05 |
| Protein, g/L | 73.9 (5.4); n = 35,490 | 74.3 (4.9); n = 12,386 | 73.8 (5.6); n = 23,104 | 0.1 | 74.4 (5.0); n = 23,401 | 74.3 (4.9); n = 12,387 | 74.5 (5.0); n = 11,014 | 0.05 |
| Creatinine, μmol/L | 92.5 (71.5); n = 49,633 | 79.0 (28.9); n = 15,520 | 98.6 (83.2); n = 34,113 | 0.31 a | 80.4 (33.0); n = 29,687 | 79.0 (28.9); n = 15,514 | 82.0 (36.9); n = 14,173 | 0.09 |
| Alkaline phosphatase, U/L | 76.2 (30.1); n = 37,836 | 73.5 (26.1); n = 13,091 | 77.6 (31.9); n = 24,745 | 0.14 | 74.8 (27.2); n = 24,597 | 73.5 (26.1); n = 13,095 | 76.2 (28.3); n = 11,502 | 0.1 |
| Aspartate transaminase, U/L | 28.2 (53.4); n = 15,006 | 28.1 (26.9); n = 5161 | 28.2 (63.0); n = 9845 | <0.01 | 28.8 (30.5); n = 10,477 | 28.2 (26.9); n = 5162 | 29.4 (33.6); n = 5315 | 0.04 |
| Alanine transaminase, U/L | 29.4 (33.6); n = 32,037 | 32.1 (28.1); n = 11,145 | 28.0 (36.1); n = 20,892 | 0.13 | 32.3 (27.5); n = 20,438 | 32.1 (28.2); n = 11,145 | 32.4 (26.6); n = 9293 | 0.01 |
| Bilirubin, μmol/L | 11.3 (6.7); n = 37,645 | 11.4 (5.6); n = 13,060 | 11.2 (7.1); n = 24,585 | 0.04 | 11.4 (5.7); n = 24,545 | 11.4 (5.6); n = 13,064 | 11.3 (5.8); n = 11,481 | 0.01 |
| Lipid profiles | ||||||||
| Triglyceride, mmol/L | 1.7 (1.6); n = 46,943 | 1.8 (1.7); n = 14,910 | 1.7 (1.5); n = 32,033 | 0.06 | 1.8 (1.8); n = 28,423 | 1.8 (1.75); n = 14,910 | 1.82 (1.84); n = 13,513 | 0.01 |
| Low‐density lipoprotein, mmol/L | 2.4 (0.8); n = 46,121 | 2.37 (0.8); n = 14,658 | 2.4 (0.8); n = 31,463 | 0.04 | 2.4 (0.8); n = 27,937 | 2.37 (0.8); n = 14,657 | 2.39 (0.79); n = 13,280 | 0.03 |
| High‐density lipoprotein, mmol/L | 1.2 (0.3); n = 46,872 | 1.16 (0.31); n = 14,885 | 1.21 (0.33); n = 31,987 | 0.15 | 1.2 (0.3); n = 28,370 | 1.16 (0.31); n = 14,885 | 1.18 (0.32); n = 13,485 | 0.06 |
| Total cholesterol, mmol/L | 4.3 (1.0); n = 46,986 | 4.3 (1.0); n = 14,929 | 4.4 (1.0); n = 32,057 | 0.04 | 4.3 (1.0); n = 28,445 | 4.3 (1.0); n = 14,929 | 4.4 (1.0); n = 13,516 | 0.05 |
| Haemoglobin A1C, % | 8.1 (1.5); n = 48,920 | 8.3 (1.6); n = 15,353 | 8.0 (1.5); n = 33,567 | 0.21 a | 8.3 (1.6); n = 29,345 | 8.3 (1.57); n = 15,352 | 8.26 (1.61); n = 13,993 | 0.03 |
| Fasting glucose, mmol/L | 9.9 (3.3); n = 34,323 | 10.1 (3.2); n = 11,828 | 9.8 (3.4); n = 22,495 | 0.08 | 10.1 (3.3); n = 22,141 | 10.1 (3.2); n = 11,841 | 10.0 (3.5); n = 10,300 | 0.02 |
Abbreviations: ACEI/ARB, Angiotensin‐converting enzyme inhibitors Angiotensin receptor blockers; DPP4I, dipeptidyl peptidase‐4 inhibitor; MDRD, modification of diet in renal disease; SD, standard deviation; SGLT2I, sodium glucose cotransporter‐2 inhibitor.
a
For SMD ≥0.2.