Table 1:
Patient Characteristics on Index date for those without Cardiovascular Disease
| DPP4i N=28,628 |
GLP1RA N=28,628 |
SMD | DPP4i N=28,628 |
SGLT2i N=28,628 |
SMD | |
|---|---|---|---|---|---|---|
| Age, years* | 66.0 [57.9, 71.0] | 66.2 [57.9, 71.1] | 0.001 | 66.9 [59.1,71.5] | 67.0 [59.1,71.5] | 0.016 |
| Male, (No., %) | 26337 (92.0) | 26488 (92.1) | 0.004 | 19929 (94.1) | 19974 (94.2) | 0.003 |
| Race, (No., %) | 0.005 | 0.004 | ||||
| Other | 1117 ( 4.1) | 1146 ( 4.2) | 773 ( 3.9) | 774 ( 3.9) | ||
| Black | 5905 (21.9) | 5908 (21.8) | 4406 (21.9) | 4446 (22.1) | ||
| White | 19979 (74.0) | 20058 (74.0) | 14900 (74.2) | 14888 (74.0) | ||
| Missing Race (No., %) | 1627 ( 5.7) | 1647 ( 5.7) | 0.002 | 1091 ( 5.2) | 1092 ( 5.2) | <0.001 |
| Medication start to index date, years* | 8.5 (4.8, 12.9) | 8.5 (4.8, 12.9) | 0.004 | 8.8 [5.4, 13.2] | 8.8 [5.3, 13.2] | 0.001 |
| Co-Therapy, (No., %) | 0.005 | 0.005 | ||||
| Metformin | 2915 (10.2) | 2931 (10.2) | 3574 (16.9) | 3552(16.8) | ||
| Sulfonylurea | 1069 ( 3.7) | 1064 ( 3.7) | 1174 ( 5.5) | 1166 ( 5.5) | ||
| Insulin | 6191 (21.6) | 6249 (21.7) | 2802 (13.2) | 2814 (13.3) | ||
| Metformin + Sulfonylurea | 5283 (18.5) | 5271 (18.3) | 6676 (31.5) | 6674 (31.5) | ||
| Metformin + Insulin | 11172 (39.0) | 11253 (39.1) | 6191 (29.2) | 6231 (29.4) | ||
| Sulfonylurea + Insulin | 1997 ( 7.0) | 1991 ( 6.9) | 754 ( 3.6) | 764 ( 3.6) | ||
| Year of cohort entry, (No., %) | 0.098 | 0.054 | ||||
| 2005-2007 | 167 ( 0.6) | 309 ( 1.1) | 0 (0) | 0 (0) | ||
| 2008-2010 | 1067 (3.7) | 883 (3.1) | 0 (0) | 0 (0) | ||
| 2011-2013 | 2340 (8.2) | 2476 (8.6) | 110 ( 0.5) | 59 ( 0.3) | ||
| 2014-2016 | 7223 (25.2) | 7314 (25.4) | 2958 (14.0) | 2966 (13.9) | ||
| 2017-2019 | 17831 (62.3) | 17777 (61.8) | 18103 (85.5) | 18175 (85.7) | ||
| Clinical Variables | ||||||
| Body Mass Index, kg/m2 * | 34.3 [30.4, 38.9] | 34.6 [30.7, 39.2] | 0.039 | 32.8 [29.1,37.2] | 33.0 [29.3, 37.4] | 0.023 |
| Missing BMI Measure (No., %) | 6276 (21.9) | 6264 (21.8) | 0.003 | 4838 (22.9) | 4779 (22.5) | 0.007 |
| Systolic Blood Pressure, mm/Hg * | 133 [123, 143] | 133 [123, 143] | 0.004 | 133 [124, 143] | 133 [123, 143] | 0.003 |
| Diastolic Blood Pressure mm/Hg * | 76 [70, 82] | 76 [70, 83] | 0.001 | 77 [70, 83] | 77 [70, 83] | 0.005 |
| Missing Diastolic Blood Pressure (No., %) | 688 (2.4) | 675 (2.3) | 0.004 | 410 ( 1.9) | 379 ( 1.8) | 0.011 |
| Echocardiogram Ejection Fraction Category (No., %) | 0.019 | 0.018 | ||||
| Normal < 50% | 5044 (17.6) | 5129 (17.8) | 3724 (17.6) | 3756 (17.7) | ||
| Indeterminate 40-49% | 676 (2.4) | 664 (2.3) | 507 (2.4) | 515 (2.4) | ||
| Reduced/Severe < 40% | 630 (2.2) | 652 (2.3) | 519 (2.5) | 551 (2.6) | ||
| Missing/Unavailable | 22277 (77.8) | 22314 (77.6) | 0.005 | 16421(77.6) | 16378 (77.3) | 0.007 |
| Laboratory Variables | ||||||
| HbA1c, % * | 8.4 [7.6, 9.6] | 8.6 [7.6, 9.7] | 0.004 | 8.4 [7.7, 9.4] | 8.5 [7.7, 9.5] | 0.013 |
| Missing HbA1c (No., %) | 2152 (7.5) | 2095 ( 7.3) | 0.009 | 1560 ( 7.4) | 1510 ( 7.1) | 0.01 |
| Hemoglobin, g/dL * | 14.1 [13.1, 15.1] | 14.1 [13.1, 15.1] | 0.005 | 14.3 [13.3, 15.2] | 14.3 [13.3, 15.2] | 0.003 |
| Missing Hemoglobin (No.,%) | 2905 (10.1) | 2902 (10.1) | 0.002 | 1841 ( 8.7) | 1803 ( 8.5) | 0.007 |
| Estimated Glomerular Filtration rate, ml/min/1.73 m2 * | 79.5 [60.5, 95.8] | 79.5 [60.1, 95.7] | 0.002 | 83 [68, 95] | 82 [67, 96] | 0.004 |
| Serum Creatinine mg/dL * | 1.03 [0.89, 1.30] | 1.03 [0.89, 1.30] | 0.001 | 1.00 [0.87, 1.19] | 1.00 [0.87, 1.20] | 0.016 |
| Missing Creatinine (No.,%) | 1905 ( 6.7) | 1893 ( 6.6) | 0.003 | 1241 ( 5.9) | 1172 ( 5.5) | 0.014 |
| Low Density Lipoprotein mg/dL * | 81 [63, 105] | 81 [63, 105] | 0.003 | 81 [62, 105] | 81 [62, 106] | <0.001 |
| Missing Low Density Lipoprotein (No., %) | 1984 (6.9) | 1945 (6.8) | 0.007 | 1239 ( 5.9) | 1175 ( 5.5) | 0.013 |
| Urine protein on urinalysis (No., %) | 0.002 | 0.009 | ||||
| Negative | 11585 (40.5) | 11615 (40.4) | 8851 (41.8) | 8879 (41.9) | ||
| trace or 1+ | 3302 (11.5) | 3321 (11.5) | 2020 ( 9.5) | 2048 ( 9.7) | ||
| 2+ | 1879 ( 6.6) | 1901 ( 6.6) | 1117 ( 5.3) | 1142 ( 5.4) | ||
| 3+/4+/trace to 4+ | 527 ( 1.8) | 529 ( 1.8) | 220 ( 1.0) | 227 ( 1.1) | ||
| Missing Urine protein measure (No., %) | 11335 (39.6) | 11392 (39.6) | 8962 (42.3) | 8904 (42.0) | ||
| Microalbumin to Creatinine ratio (MACR) stage N (No., %) | 0.006 | 0.008 | ||||
| A1 (<30 mg/g- normal to mild increase albuminuria) | 11676 (40.8) | 11769 (40.9) | 9161 (43.3) | 9182 (43.3) | ||
| A2 (30-300 mg/g- moderate increase albuminuria) | 5284 (18.5) | 5348 (18.6) | 3993 (18.9) | 4037 (19.0) | ||
| A3 and positive (>300 mg/g severely increased albuminuria) | 2068 ( 7.2) | 2078 ( 7.2) | 1310 (6.2) | 1334 ( 6.3) | ||
| Missing MACR measure | 9599 (33.5) | 9564 (33.3) | 6706 (31.7) | 6647 (31.4) | ||
| Baseline Comorbidities (No., %) ‡ | ||||||
| Cardiovascular conditions | ||||||
| Congestive Heart Failure | 1366 ( 4.8) | 1383 ( 4.8) | 0.002 | 978 ( 4.6) | 991.4 ( 4.7) | 0.003 |
| Arrhythmias | 1557 ( 5.4) | 1558 ( 5.4) | 0.001 | 950 ( 4.5) | 944.3 ( 4.5) | 0.002 |
| Cardiac valve disease | 392 ( 1.4) | 395 ( 1.4) | <0.001 | 322 ( 1.5) | 322.4 ( 1.5) | <0.001 |
| Pulmonary Conditions | ||||||
| Smoking | 2978 (10.4) | 2987 (10.4) | <0.001 | 1816 ( 8.6) | 1831 ( 8.6) | 0.002 |
| Chronic Obstructive Pulmonary Disease | 3868 (13.5) | 3888 (13.5) | <0.001 | 2691 (12.7) | 2694 (12.7) | <0.001 |
| History of Respiratory failure | 713 ( 2.5) | 712 ( 2.5) | 0.001 | 468 ( 2.2) | 476 ( 2.2) | 0.002 |
| Neuro- Psychiatric Conditions | ||||||
| Serious Mental Illness | 9440 (33.0) | 9532 (33.1) | 0.004 | 6277 (29.6) | 6318 (29.8) | 0.003 |
| Parkinson's | 209 ( 0.7) | 215 ( 0.7) | 0.002 | 149 ( 0.7) | 146 ( 0.7) | 0.002 |
| Retinopathy | 3642 (12.7) | 3666 (12.7) | 0.001 | 2183 (10.3) | 2233 (10.5) | 0.007 |
| Infectious Conditions | ||||||
| History of Sepsis | 494 ( 1.7) | 488 ( 1.7) | 0.002 | 267 ( 1.3) | 263 ( 1.2) | 0.002 |
| History of Pneumonia | 502 ( 1.8) | 499 ( 1.7) | 0.001 | 316 ( 1.5) | 313 ( 1.5) | 0.001 |
| HIV | 130 ( 0.5) | 134 ( 0.5) | 0.002 | 95 ( 0.4) | 97 ( 0.5) | 0.001 |
| Urinary tract infection | 1266 ( 4.4) | 1274 ( 4.4) | <0.001 | 626 ( 3.0) | 625 ( 2.9) | <0.001 |
| Osteomyelitis | 229 ( 0.8) | 222 ( 0.8) | 0.003 | 100 ( 0.5) | 101 ( 0.5) | 0.001 |
| Other serious illness and disabilities | ||||||
| Malignancy | 2729 ( 9.5) | 2761 ( 9.6) | 0.002 | 2119 (10.0) | 2119 (10.0) | 0.001 |
| Liver disease | 1306 ( 4.6) | 1323 ( 4.6) | 0.002 | 1108 (5.2) | 1133 (5.3) | 0.005 |
| History of Kidney disease | 7 ( 0.0) | 7 ( 0.0) | <0.001 | 1 (0.0) | 1 (0.0) | 0.003 |
| Osteoporosis | 197 ( 0.7) | 195 ( 0.7) | 0.001 | 130 ( 0.6) | 128 ( 0.6) | 0.001 |
| Falls | 248 ( 0.9) | 246 ( 0.9) | 0.001 | 197 ( 0.9) | 194 ( 0.9) | 0.002 |
| Fractures | 510 ( 1.8) | 506 ( 1.8) | 0.002 | 323 ( 1.5) | 319 ( 1.5) | 0.002 |
| Amputation | 113 ( 0.4) | 115 ( 0.4) | <0.001 | 56 ( 0.3) | 58 ( 0.3) | 0.001 |
| Use of Medications (No., %) | ||||||
| ACE Inhibitors | 14682 (51.3) | 14739 (51.2) | 0.001 | 11031 (52.1) | 11061 (52.2) | 0.001 |
| Angiotensin Receptor Blockers | 6916 (24.2) | 6960 (24.2) | 0.001 | 4908 (23.2) | 4921 (23.2) | 0.001 |
| Beta Blockers | 10508 (36.7) | 10564 (36.7) | 0.001 | 7697 (36.4) | 7713 (36.4) | <0.001 |
| Calcium Channel Blockers | 8852 (30.9) | 8920 (31.0) | 0.002 | 6385 (30.2) | 6404 (30.2) | 0.001 |
| Thiazide/potassium sparing diuretics | 9886 (34.5) | 9945 (34.6) | 0.001 | 6914 (32.7) | 6947 (32.8) | 0.002 |
| Loop diuretics | 4215 (14.7) | 4218 (14.7) | 0.002 | 2252 (10.6) | 2259 (10.7) | 0.001 |
| Other antihypertensives | 7996 (27.9) | 8020 (27.9) | 0.001 | 5499 (26.0) | 5459 (25.8) | 0.005 |
| Lipid-lowering statins | 22020 (76.9) | 22159 (77.1) | 0.003 | 16680 (78.8) | 16724 (78.9) | 0.002 |
| Non-statin lipid-lowering agents | 4407 (15.4) | 4427 (15.4) | <0.001 | 3019 (14.3) | 3003 (14.2) | 0.003 |
| Anti-arrhythmic digoxin and inotropes | 1387 ( 4.8) | 1397 ( 4.9) | <0.001 | 1190 ( 5.6) | 1177 ( 5.6) | 0.003 |
| Anticoagulants | 2114 ( 7.4) | 2129 ( 7.4) | 0.001 | 1686 ( 8.0) | 1677 ( 7.9) | 0.002 |
| Nitrates | 841 ( 2.9) | 834 ( 2.9) | 0.002 | 617( 2.9) | 616 ( 2.9) | <0.001 |
| Aspirin | 5641 (19.7) | 5723 (19.9) | 0.005 | 4228 (20.0) | 4296 (20.3) | 0.007 |
| Platelet inhibitors | 949 ( 3.3) | 941 ( 3.3) | 0.002 | 857 ( 4.1) | 848 ( 4.0) | 0.003 |
| Antipsychotics | 1853 ( 6.5) | 1879 ( 6.5) | 0.002 | 1284 ( 6.1) | 1287 ( 6.1) | <0.001 |
| Oral Glucocorticoids | 2749 ( 9.6) | 2734 ( 9.5) | 0.003 | 1970 ( 9.3) | 1921 ( 9.1) | 0.008 |
| Indicators of Utilization (No.,%) | ||||||
| Hospitalization within year (Veterans Health) | 2014 (7.0) | 2030 (7.1) | 0.001 | 1247 ( 5.9) | 1284 ( 6.1) | 0.007 |
| Hospitalizations within 30 days (Veterans Health) | 301 (1.1) | 303 (1.1) | <0.001 | 208 ( 1.0) | 216 ( 1.0) | 0.004 |
| Hospitalizations within year (Medicaid/ Medicare) | 1121 (3.9) | 1113 (3.9) | 0.002 | 649 ( 3.1) | 630 ( 3.0) | 0.006 |
| Hospitalizations within 30 days (Medicaid/ Medicare) | 118 (0.4) | 114 (0.4) | 0.002 | 72 ( 0.3) | 73 ( 0.3) | <0.001 |
| Medicaid insurance use in last year | 638 (2.2) | 615 (2.1) | 0.006 | 262 ( 1.2) | 252 ( 1.2) | 0.004 |
| Medicare insurance use in last year | 11733 (41.0) | 11499 (40.0) | 0.02 | 8286 (39.1) | 7886 (37.2) | 0.04 |
| Nursing home encounters | 78 (0.3) | 80 (0.3) | 0.001 | 45 ( 0.2) | 48 ( 0.2) | 0.002 |
| Outpatient visits in last year * | 6.0 [3.0, 10.0] | 6.0 [3.0, 11.0] | 0.012 | 5 [2, 9] | 5 [2, 10] | 0.016 |
| Outpatient Medications§ | 5.0 [3.0, 6.0] | 5.0 [4.0, 6.0] | 0.004 | 4 [3, 6] | 4 [3, 6] | 0.001 |
| Medicare Advantage Use | ∣ 7336 (25.6) | 7271 (25.3) | 0.008 | 5047 (23.8) | 4880 (23.0) | 0.019 |
*
Median and IQR = Interquartile range
†
See Supplemental Figures 4 and 5 for the plot of the mean Standardized differences of the pre- matched and matched cohort.
‡
Definitions of co-morbidities in Supplemental Table 2
§
xcludes Diabetes medications, topical and ophthalmic medications and medical supplies)