Patient characteristics on index date of kidney function decline and at 361 days after the index date for persistent patients
| Characteristic | No. (%) of patients in propensity score–weighted cohort at index date* | SMD† | No. (%) of patients in propensity score–weighted cohort at 361 d | SMD† | ||
|---|---|---|---|---|---|---|
| Metformin n = 24 883 | Sulfonylureas n = 24 998 | Metformin n = 12 571 | Sulfonylureas n = 12 637 | |||
| Age, yr, median (IQR) | 70.7 (63.7–78.1) | 70.5 (63.7–78.1) | 0.001 | 72.5 (65.4–79.5) | 72.2 (65.3–79.4) | 0.003 |
| Sex, male | 24362 (97.9) | 24476 (97.9) | 0.001 | 12334 (98.1) | 12406 (98.2) | 0.004 |
| Race | ||||||
| White | 20908 (84.0) | 21007 (84.0) | 0.002 | 10918 (86.9) | 10982 (86.9) | 0.002 |
| Black | 3503 (14.1) | 3512 (14.0) | 1424 (11.3) | 1430 (11.3) | ||
| Other‡ | 472 (1.9) | 479 (1.9) | 229 (1.8) | 226 (1.8) | ||
| Time from cohort entry to kidney threshold, mo, median (IQR) | 14.2 (5.9–30.7) | 14.3 (6.1–30.9) | 0.014 | 28.4 (18.9–45.4) | 28.6 (19.0–45.6) | 0.009 |
| Year reached kidney threshold | ||||||
| 2002–2003 | 2815 (11.3) | 2808 (11.2) | 0.027 | 1568 (12.5) | 1545 (12.2) | 0.038 |
| 2004–2005 | 4308 (17.3) | 4268 (17.1) | 2236 (17.8) | 2234 (17.7) | ||
| 2006–2007 | 5005 (10.1) | 5216 (20.9) | 2722 (21.7) | 2853 (22.6) | ||
| 2008–2009 | 3726 (15.0) | 3781(15.1) | 1983 (15.8) | 1999 (15.8) | ||
| 2010–2011 | 3291 (13.2) | 3207 (12.8) | 1737 (13.8) | 1673 (13.2) | ||
| 2012–2013 | 2603 (10.5) | 2556 (10.2) | 1281(10.2) | 1254 (9.9) | ||
| 2014–2015 | 2164 (8.7) | 2181 (8.7) | 1038 (8.2) | 1076 (8.5) | ||
| 2016 | 971 (3.9) | 981 (3.9) | 5 (0.0) | 3 (0.0) | ||
| Laboratory variables | ||||||
| HbA1c, %, median (IQR) | 6.5 (6.1–7.1) | 6.5 (6.1–7.2) | 0.007 | 6.5 (6.1–7.0) | 6.50 (6.0–7.1) | 0.007 |
| Missing HbA1C measure | 1011 (4.1) | 994 (4.0) | 0.004 | 503 (4.0) | 488 (3.9) | |
| Historical eGFR before kidney threshold, mL/min/1.73 m2, median (IQR)§ | 69.3 (64.5–76.6) | 69.3 (64.5–76.6) | 0.001 | – | – | |
| eGFR at kidney threshold, mL/min/1.73 m2, median (IQR) | 55.6 (51.4–58.0) | 55.6 (51.4–58.0) | 0.002 | 55.9 (52.2–58.1) | 55.8 (52.2–58.2) | 0.003 |
| eGFR at 361 days, mL/min/1.73 m2, median (IQR) | – | – | 63.5 (55.8–72.3) | 63.7 (55.7–72.3) | 0.007 | |
| Missing eGFR | 293 (1.2) | 296 (1.2) | 0.001 | 964 (7.7) | 957 (7.6) | 0.004 |
| Hemoglobin, g/dL, median (IQR) | 14.0 (13.0–15.1) | 14.1 (13.0–15.1) | 0.003 | 13.9 (12.9–14.9) | 14.0 (12.9–15.0) | 0.004 |
| Missing hemoglobin | 1507 (6.1) | 1503 (6.0) | 0.002 | 777 (6.2) | 792 (6.3) | 0.003 |
| Low-density lipoprotein, mmol/L, median (IQR) | 2.28 (1.81–2.82) | 2.28 (1.81–2.82) | 0.002 | 2.18 (1.76–2.64) | 2.18 (1.76–2.67) | 0.001 |
| Missing low-density lipoprotein measure | 779 (3.1) | 781 (3.1) | < 0.001 | 310 (2.5) | 309 (2.4) | 0.004 |
| Microalbumin-to-creatinine ratio stage | ||||||
| Normal (< 30 mg/g) | 9616 (38.6) | 9670 (38.7) | 0.003 | 5261 (41.9) | 5305 (42.0) | 0.003 |
| Microalbuminuria (30–300 mg/g) | 2775 (11.2) | 2771.0 (11.1) | 1516 (12.1) | 1523 (12.1) | ||
| Macroalbuminuria (> 300 mg/g) | 788 (3.2) | 781.6 (3.1) | 370 (2.9) | 373 (3.0) | ||
| Missing microalbumin-to-creatinine ratio | 11703 (47.0) | 11775 (47.1) | 5424 (43.1) | 5436 (43.0) | ||
| Proteinuria by urinalysis | ||||||
| Negative | 11736 (47.2) | 11787 (47.2) | 0.002 | 6101 (48.5) | 6129 (48.5) | 0.002 |
| Urine protein trace or 1+ | 3533 (14.2) | 3561 (14.2) | 1700 (13.5) | 1711 (13.5) | ||
| Proteinuria present at 2+ | 831 (3.3) | 838 (3.4) | 330 (2.6) | 330 (2.6) | ||
| Proteinuria present at 3+ or 4+ | 336 (1.3) | 336 (1.3) | 127 (1.0) | 126 (1.0) | ||
| Unknown urine protein measure | 8446 (33.9) | 8476 (33.9) | 4313 (34.3) | 4341 (34.4) | ||
| Clinical variables | ||||||
| Systolic blood pressure, mm Hg, median (IQR) | 131 (119–142) | 131 (119–142) | 0.002 | 132 (120–142) | 132 (121–142) | 0.005 |
| Diastolic blood pressure, mm Hg, median (IQR) | 72 (64–80) | 72 (64–80) | 0.001 | 72 (64–79) | 72 (64–79) | 0.001 |
| BMI, median (IQR) | 30.3 (27.0–34.4) | 30.3 (27.0–34.3) | 0.003 | 30.2 (27.0–34.2) | 30.2 (27.0–34.1) | 0.001 |
| Missing BMI measure | 4688 (18.8) | 4719 (18.9) | 0.001 | 2290 (18.2) | 2306 (18.3) | 0.003 |
| Baseline comorbidities | ||||||
| Malignant disease¶ | 2971 (11.9) | 2990 (12.0) | 0.001 | 1622 (12.9) | 1622 (12.8) | 0.002 |
| Liver disease | 625 (2.5) | 621 (2.5) | 0.002 | 230 (1.8) | 229 (1.8) | 0.001 |
| HIV | 89 (0.4) | 90 (0.4) | 0.001 | 39 (0.3) | 40 (0.3) | 0.001 |
| Congestive heart failure | 3051 (12.3) | 3071 (12.3) | 0.001 | 1580 (12.6) | 1592 (12.6) | 0.001 |
| Cardiovascular disease | 7935 (31.9) | 8006 (32.0) | 0.003 | 3987 (31.7) | 4019 (31.8) | 0.002 |
| Stroke | 831 (3.3) | 827 (3.3) | 0.002 | 399 (3.2) | 401 (3.2) | < 0.01 |
| Transient ischemic attack | 322 (1.3) | 332 (1.3) | 0.003 | 155 (1.2) | 153 (1.2) | 0.002 |
| Serious mental illness** | 4957 (19.9) | 5035 (20.1) | 0.005 | 2401 (19.1) | 2430 (19.2) | 0.003 |
| Smoking | 3045 (12.2) | 3068 (12.3) | 0.001 | 1262 (10.0) | 1263 (10.0) | 0.002 |
| Chronic obstructive pulmonary disease | 4284 (17.2) | 4321 (17.3) | 0.002 | 2157 (17.2) | 2166 (17.1) | < 0.01 |
| History of respiratory failure | 821 (3.3) | 821 (3.3) | 0.001 | 543 (4.3) | 533 (4.2) | 0.005 |
| History of sepsis | 406 (1.6) | 414 (1.7) | 0.002 | 291 (2.3) | 291 (2.3) | 0.001 |
| History of pneumonia | 1074 (4.3) | 1092 (4.4) | 0.003 | 648 (5.2) | 640 (5.1) | 0.004 |
| Arrhythmia | 4387 (17.6) | 4418 (17.7) | 0.001 | 2399 (19.1) | 2414 (19.1) | < 0.01 |
| Cardiac valve disease | 919 (3.7) | 929 (3.7) | 0.001 | 497 (4.0) | 503 (4.0) | 0.002 |
| Parkinson disease | 234 (0.9) | 237 (0.9) | 0.001 | 162 (1.3) | 158 (1.3) | 0.003 |
| Urinary tract infection | 1055 (4.2) | 1067 (4.3) | 0.001 | 640 (5.1) | 645 (5.1) | 0.001 |
| Osteomyelitis | 156 (0.6) | 154 (0.6) | 0.002 | 65 (0.5) | 64 (0.5) | 0.002 |
| Osteoporosis | 200 (0.8) | 206 (0.8) | 0.002 | 118 (0.9) | 115 (0.9) | 0.003 |
| Falls | 57 (0.2) | 59 (0.2) | 0.002 | 59 (0.5) | 57 (0.4) | 0.003 |
| Fractures | 556 (2.2) | 556 (2.2) | 0.001 | 315 (2.5) | 313 (2.5) | 0.002 |
| Amputation | 118 (0.5) | 123 (0.5) | 0.002 | 55 (0.4) | 55 (0.4) | 0.001 |
| Retinopathy | 286 (1.1) | 287 (1.1) | < 0.001 | 117 (0.9) | 121 (1.0) | 0.003 |
| Use of medications | ||||||
| Angiotensin-converting enzyme inhibitors | 15958 (64.1) | 16080 (64.3) | 0.004 | 7623 (60.6) | 7690 (60.9) | 0.004 |
| Angiotensin II receptor blockers | 2904 (11.7) | 2904 (11.6) | 0.002 | 1647 (13.1) | 1644 (13.0) | 0.003 |
| β-blockers | 12699 (51.0) | 12770 (51.1) | 0.001 | 6533 (52.0) | 6565 (51.9) | < 0.01 |
| Calcium-channel blockers | 7417 (29.8) | 7454 (29.8) | < 0.001 | 3801 (30.2) | 3820 (30.2) | < 0.01 |
| Thiazide- and potassium-sparing diuretics | 10072 (40.5) | 10169 (40.7) | 0.004 | 4531 (36.0) | 4578 (36.2) | 0.004 |
| Loop diuretics | 5059 (20.3) | 5087 (20.3) | < 0.001 | 2433 (19.4) | 2448 (19.4) | 0.001 |
| Other antihypertensive medications | 6873 (27.6) | 6887 (27.6) | 0.002 | 3834 (30.5) | 3834 (30.3) | 0.003 |
| Statin lipid-lowering drugs | 16763 (67.4) | 16917 (67.7) | 0.007 | 9059 (72.1) | 9119 (72.2) | 0.002 |
| Nonstatin lipid-lowering agents | 4237 (17.0) | 4264 (17.1) | 0.001 | 2275 (18.1) | 2280 (18.0) | 0.002 |
| Antiarrhythmic drugs, digoxin and inotropes | 2313 (9.3) | 2321 (9.3) | < 0.001 | 1072 (8.5) | 1078 (8.5) | < 0.01 |
| Anticoagulant drugs and platelet inhibitors | 2578 (10.4) | 2588 (10.4) | < 0.001 | 1386 (11.0) | 1394 (11.0) | < 0.01 |
| Nitrates | 3652 (14.7) | 3689 (14.8) | 0.002 | 1716 (13.6) | 1739 (13.8) | 0.003 |
| ASA | 5332 (21.4) | 5385 (21.5) | 0.003 | 2533 (20.1) | 2570 (20.3) | 0.005 |
| Non-ASA platelet inhibitors | 2643 (10.6) | 2660 (10.6) | 0.001 | 1329 (10.6) | 1343 (10.6) | 0.002 |
| Antipsychotic drugs | 1662 (6.7) | 1685 (6.7) | 0.003 | 747 (5.9) | 745 (5.9) | 0.002 |
| Oral glucocorticoids | 1823 (7.3) | 1845 (7.4) | 0.002 | 894 (7.1) | 892 (7.1) | 0.002 |
| Indicators of health care use†† | ||||||
| Admitted to hospital within year (Veterans Health) | 3550 (14.3) | 3600 (14.4) | 0.004 | 1510 (12.0) | 1538 (12.2) | 0.005 |
| Admitted to hospital in 30 days (Veterans Health) | 934 (3.8) | 953 (3.8) | 0.003 | 188 (1.5) | 187 (1.5) | 0.001 |
| Admitted to hospital within year (Medicare/Medicaid) | 2851 (11.5) | 2860 (11.4) | < 0.001 | 1521 (12.1) | 1507 (11.9) | 0.005 |
| Admitted to hospital in 30 days (Medicare/Medicaid) | 450 (1.8) | 461 (1.8) | 0.003 | 197 (1.6) | 198 (1.6) | < 0.01 |
| Medicaid use in previous year | 298 (1.2) | 307 (1.2) | 0.003 | 143 (1.1) | 142 (1.1) | 0.001 |
| Medicare use in previous year | 9128 (36.7) | 9129 (36.5) | 0.003 | 5221 (41.5) | 5213 (41.3) | 0.006 |
| Nursing home encounter in previous year | 97 (0.4) | 102 (0.4) | 0.003 | 66 (0.5) | 67 (0.5) | < 0.01 |
| Medicare Advantage use | 3979 (16.0) | 3998 (16.0) | < 0.001 | 2498 (19.9) | 2517 (19.9) | 0.001 |
Note: ASA = acetylsalicylic acid, BMI = body mass index, eGFR = estimated glomerular filtration rate, IQR = interquartile range, SMD = standardized mean difference.
↵* Unless indicated otherwise.
↵† Standardized mean differences are the absolute difference in means or percentage divided by an evenly weighted pooled standard deviation, or the difference between groups in number of standard deviations. In the weighted cohort, all standardized differences were less than 0.01, suggesting there were no important imbalances.
↵‡ Other races include American Indian or Alaska Native, Asian, and Native Hawaiian or Pacific Islander.
↵§ Historical eGFR is the eGFR before the patient met the inclusion criteria of eGFR < 60 mL/min/1.73 m2; eGFR at kidney threshold indicates the eGFR when the patient met the inclusion criteria of eGFR < 60 mL/min/1.73 m2.
↵¶ Malignant disease includes all types of cancer except nonmelanoma skin cancer.
↵** Serious mental illness included schizophrenia, depression, bipolar disorder, dementia and post-traumatic stress disorder.
↵†† The Veterans Health Administration provides health care coverage for those who serve their country through military services. Medicare and Medicaid health services are federal health care programs for eligible people older than 65 years. Medicare Advantage is a Medicare plan offered by private insurers that provides hospital, outpatient and (usually) prescription drug coverage, supplanting benefits under other Medicare plans.