Table 1.
Characteristics of patients at the time of treatment intensification
| Characteristics | Full Cohort | Propensity matched Cohort | ||||
|---|---|---|---|---|---|---|
|
| ||||||
|
Metformin+ Sulfonylurea N=39,990 |
Metformin+ Insulin N=2948 |
Standardized differences* |
Metformin+ Sulfonylurea N=12180 |
Metformin+ Insulin N=2436 |
Standardized differences* |
|
| Age, median (IQR) | 61 (56, 69) | 60 (54, 67) | −0.13 | 60 (54, 68) | 60 (55, 68) | 0.02 |
| Male N (%) | 38345 (96) | 2787 (95) | −0.07 | 11521 (95) | 2315 (95) | 0.02 |
| Race, N (%) | ||||||
| White | 29458 (74) | 2023 (69) | −0.11 | 8612 (71) | 1726 (71) | 0.00 |
| Black | 5161 (13) | 571 (19) | 0.19 | 2028 (17) | 400 (16) | −0.01 |
| Hispanic/ Other | 1832 (5) | 124 (4) | −0.02 | 512 (4) | 111 (5) | 0.02 |
| Missing | 3539 (9) | 230 (8) | −0.04 | 1028 (8) | 199 (8) | −0.01 |
| Time to intensification†, months median (IQR) | 18 (7, 34) | 14 (5, 30) | −0.13 | 14 (6, 31) | 14 (5, 30) | −0.01 |
| HbA1c, % median (IQR) | 7.6 (7.0, 8.6) | 8.5 (7.0, 10.7) | 0.54 | 8.1 (7.2, 9.9) | 8.1 (6.9,9.9) | −0.07 |
| Missing measurement, N (%) | 5470 (14) | 573 (19) | 0.17 | 2315 (19) | 470 (19) | 0.01 |
| Low Density Lipoprotein mg/dL, median (IQR) | 87 (70, 110) | 87 (67, 113) | −0.02 | 86 (67, 110) | 87 (67, 113) | 0.02 |
| Missing measurement, N (%) | 8492 (21) | 851 (29) | 0.19 | 3408 (28) | 694 (28) | 0.01 |
| Creatinine mg/dL, median (IQR) | 1.0 (0.9, 1.1) | 1.0 (0.9, 1.2) | 0.04 | 1.0 (0.9, 1.1) | 1.0 (0.9, 1.2) | 0.00 |
| Glomerular filtration rate ml/min, median (IQR) | 81 (70, 95) | 82 (69, 100) | 0.06 | 82 (70, 98) | 82 (70, 98) | 0.01 |
| Missing measurement, N (%) | 5978 (15) | 555 (19) | 0.11 | 2372 (19) | 468 (19) | −0.01 |
| Proteinuria, N (%) negative | 20909 (52) | 1489 (50) | 6044 (50) | 1214 (50) | ||
| trace through 4+ | 7468 (19) | 615 (21) | 0.01 | 2534 (20) | 503 (20) | 0.00 |
| Missing measurement, N (%) | 11613 (29) | 844 (29) | 0.01 | 3602 (30) | 719 (30) | 0.00 |
| Systolic Blood pressure mm/Hg, median (IQR) | 132 (122, 143) | 131 (120, 142) | −0.08 | 131 (120, 143) | 131 (120, 142) | 0.01 |
| Diastolic Blood pressure mm/Hg, median (IQR) | 77 (70, 84) | 76 (68, 83) | −0.07 | 76 (68, 83) | 76 (68, 84) | −0.01 |
| Missing measurement, N (%) | 1689 (4) | 187 (6) | 0.10 | 788 (6) | 159 (7) | 0.00 |
| Body Mass Index (kilograms/meter2), median (IQR) | 32.5(28.9,36.7) | 32.4 (28.3, 37.0) | −0.04 | 32.3(28.6,37.0) | 32.6(28.4,37.1) | 0.00 |
| Missing measurement, N (%) | 2098 (5) | 236 (8) | 0.12 | 961 (8) | 191 (8) | 0.00 |
| Baseline Co-morbidities N (%)‡ | ||||||
| Malignancy | 3059 (8) | 273 (9) | 0.06 | 1115 (9) | 223 (9) | 0.00 |
| Liver/ respiratory failure | 1156 (3) | 213 (7) | 0.25 | 668 (5) | 117 (5) | −0.04 |
| HIV | 125 (0.3) | 24 (0.8) | 0.09 | 69 (0.6) | 14 (0.6) | 0.00 |
| Congestive heart failure | 2222 (6) | 306 (10) | 0.21 | 1053 (9) | 209 (9) | 0.00 |
| Cardiovascular disease | 11849 (30) | 1056 (36) | 0.14 | 4125 (34) | 825 (34) | 0.00 |
| Serious mental illness | 11162 (28) | 1028 (35) | 0.15 | 3878 (32) | 768 (32) | −0.01 |
| Smoking | 7719 (19) | 685 (23) | 0.10 | 2581 (21) | 528 (22) | 0.01 |
| Chronic Obstructive Pulmonary Disease/ Asthma | 6114 (15) | 634 (22) | 0.17 | 2378 (20) | 481 (20) | 0.01 |
| Cardiac valve disease | 766 (2) | 84 (3) | 0.07 | 296 (2) | 62 (2) | 0.01 |
| Arrhythmia | 3449 (9) | 338 (11) | 0.10 | 1274 (10) | 255 (10) | 0.00 |
| Parkinson’s | 192 (0.5) | 36 (1) | 0.10 | 107 (0.9) | 21 (0.9) | 0.00 |
| Year N (%) | 0.14 | −0.03 | ||||
| 2002–03 | 1354 (3) | 104 (3) | 474 (4) | 93 (4) | ||
| 2004 | 3047 (8) | 191 (6) | 837 (7) | 171 (7) | ||
| 2005 | 4698 (12) | 282 (10) | 1171 (10) | 250 (10) | ||
| 2006 | 6737 (17) | 450 (15) | 1848 (15) | 379 (16) | ||
| 2007 | 7659 (19) | 451 (15) | 1895 (16) | 401 (16) | ||
| 2008 | 6544 (16) | 546 (19) | 2209 (18) | 428 (18) | ||
| 2009 | 5162 (13) | 475 (16) | 1915 (16) | 369 (15) | ||
| 2010 | 3691 (9) | 353 (12) | 1463 (12) | 275 (11) | ||
| 2011 | 1098 (3) | 96 (3) | 368 (3) | 70 (3) | ||
| Use of Medications N (%) | ||||||
| ACE Inhibitors or ARBs | 28685 (72) | 2072 (70) | −0.03 | 8576 (70) | 1727 (71) | 0.01 |
| Anti hypertensive medications | 28945 (72) | 2147 (73) | 0.01 | 8894 (73) | 1762 (72) | −0.02 |
| Statin and non-statin lipid lowering agents | 32206 (81) | 2210 (75) | −0.14 | 9250 (76) | 1858 (76) | 0.01 |
| Anti-arrhythmics, digoxin and other inotropes | 569 (1) | 78 (3) | 0.10 | 274 (2) | 57 (2) | 0.01 |
| Anticoagulants, platelet inhibitors | 4603 (12) | 482 (16) | 0.15 | 1849 (15) | 363 (15) | −0.01 |
| Nitrates | 3821 (10) | 376 (13) | 0.11 | 1472 (12) | 297 (12) | 0.00 |
| Aspirin | 9441 (24) | 872 (30) | 0.14 | 3411 (28) | 666 (27) | −0.02 |
| Loop Diuretics | 4204 (11) | 545 (18) | 0.25 | 2022 (17) | 395 (16) | −0.01 |
| Antipsychotics | 3254 (8) | 405 (14) | 0.20 | 1436 (12) | 279 (11) | −0.01 |
| Indicators of health care utilization N (%) | ||||||
| Hospitalized in last year | 5692 (14) | 1023 (35) | 0.57 | 3274 (27) | 631 (26) | −0.03 |
| Hospitalized in the 90 days prior to intensification | 2286 (6) | 679 (23) | 0.06 | 1732 (14) | 334 (14) | −0.02 |
| Nursing Home encounter in last year | 38 (0.1) | 11 (0.4) | 0.08 | 24 (0.2) | 4 (0.2) | −0.01 |
| Outpatient Visits in past year | 6 (4, 10) | 7 (4, 12) | 0.15 | 7 (4, 12) | 7 (4, 12) | −0.03 |
| Medicare use in last year | 11349 (28) | 1066 (36) | 0.17 | 4191 (34) | 843 (35) | 0.00 |
| Medicaid use in last year | 1046 (3) | 202 (7) | 0.25 | 590 (5) | 122 (5) | 0.01 |
*
Standardized differences are the absolute difference in means or percent divided by an evenly weighted pooled standard deviation, or the difference between groups in number of standard deviations. All P values in the unmatched cohort demonstrated statistically significant differences at p<0.001. In the matched cohort all standardized differences were statistically insignificant except HbA1c at p=0.05.
†
Time to treatment intensification represents the median number of months on metformin monotherapy. It is an approximation of the duration of diabetes since patients were free of all hypoglycemic medications for 180 days prior to starting metformin.
‡
Definitions of comorbidities available in eTable 1