Table 2. Event rates and adjusted hazard ratios for primary and secondary outcomes among incident OAD users.
| Metformin (N=61,104) | Sulfonylurea (N=30,550) | Rosiglitazone (N=1923) | |
|---|---|---|---|
| Primary analysis–Persistent exposure required (PER)a | |||
| Person time (years) | 77,420 | 36,592 | 2014 |
| Number of GFR or ESRD events | 2926 | 1841 | 64 |
| Rate/1000 person-years | 3.8 | 5 | 3.2 |
| aHRb (95% CI) for the primary outcome | Reference | 1.20 (1.13, 1.28) | 0.92 (0.71, 1.18) |
| Number of GFR, ESRD or death events | 3149 | 2027 | 68 |
| Rate/100 person-years | 4.1 | 5.5 | 3.4 |
| aHRb (95% CI) for the secondary outcome | Reference | 1.20 (1.13, 1.28) | 0.89 (0.69, 1.12) |
| Sensitivity analyses | |||
| PER with a more stringent definition of GFR eventc | |||
| Person time (years) | 79,197 | 37,508 | 20,44 |
| Number of GFR or ESRD events | 1390 | 908 | 34 |
| Rate/100 person-years | 1.76 | 2.42 | 1.66 |
| aHRb (95% CI) for the primary outcome | Reference | 1.17 (1.07, 1.27) | 0.90 (0.64, 1.27) |
| Number of GFR, ESRD or death events | 1622 | 1102 | 38 |
| Rate/1000 person-years | 2.05 | 2.94 | 1.86 |
| aHRb (95% CI) for the secondary outcome | Reference | 1.16 (1.08, 1.27) | 0.83 (0.60, 1.15) |
| PER adjusted for ACR | 10,293 | 4366 | 401 |
| Person Time (years) | 12291 | 4959 | 415 |
| Number of GFR or ESRD events | 461 | 245 | 11 |
| Rate/100 person-years | 3.8 | 4.9 | 2.7 |
| aHRb (95% CI) for the primary outcome | Reference | 1.22 (1.03, 1.44) | 0.67 (0.37, 1.25) |
| Number of GFR, ESRD, or death events | 493 | 263 | 12 |
| Rate/1000 person-years | 4.0 | 5.3 | 2.9 |
| aHRb (95% CI) for the secondary outcome | Reference | 1.20 (1.02, 1.41) | 0.70 (0.39, 1.24) |
| Persistent exposure not required (PENR)d | |||
| Person time (years) | 139,773 | 76,244 | 4492 |
| Number of GFR or ESRD events | 5752 | 3787 | 170 |
| Rate/100 person-years | 4.1 | 5.0 | 3.8 |
| aHRb (95% CI) for the primary outcome | Reference | 1.11 (1.06, 1.16) | 1.01 (0.87, 1.18) |
| Number of GFR, ESRD, or death events | 6403 | 4405 | 188 |
| Rate/100 person-years | 4.6 | 5.8 | 4.2 |
| aHRb (95% CI) for the secondary outcome | Reference | 1.13 (1.08, 1.18) | 0.97 (0.84, 1.12) |
Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ACR, albumin to creatinine ratio; aHR, adjusted hazard ratio; ARB, angiotensin receptor blocker; BMI, body mass index; CI, confidence interval; ESRD, end-stage renal disease; GFR, glomerular filtration rate; LDL, low-density lipoprotein; OAD, oral antidiabetic drug.
PER: considers patients persistent on their incident regimen until they have a gap in use of medications that reaches 90 days, or have added or switched to a different OAD or insulin, have a study outcome, have left the Veterans Affairs (VA), reached the end of the study or reached a creatinine of 1.5 mg/dl or higher.
Cox proportional hazards model for time to renal disease. Adjusted hazard ratio is for each exposure compared with metformin as reference. All models were adjusted for age, sex, race, fiscal year of cohort entry, number of medications, number of outpatient visits, history of hospitalization, baseline HbA1c, BMI, serum creatinine, LDL cholesterol, use of medications (ACEI or ARBs, thiazide or loop diuretics, or statins), smoking-related illness, myocardial infarction; obstructive coronary disease, or prescription for a long acting nitrate; stroke/transient ischemic attack; atrial fibrillation/flutter; mitral/aortic or rheumatic heart disease; asthma/obstructive pulmonary disease; procedures for carotid/peripheral artery revascularization or bypass or lower extremity amputation. All continuous variables were modeled as third degree polynomials.
GFR event defined as a persistent decline of 25% of baseline GFR plus reaching a GFR<60 ml/min.
PENR: patients remain in their initial OAD exposure group, regardless of their persistence on drug therapy, until a study outcome, or end of the study patients remain in their original exposure group regardless of changes in therapy after cohort entry (akin to an intent to treat analysis).