Crude and adjusted hazard ratios for low thyroid-stimulating hormone levels (< 0.4 mIU/L) associated with the use of metformin monotherapy, compared with sulfonylurea monotherapy, among 5689 patients with treated hypothyroidism and type 2 diabetes
| Variable | No. events of low TSH level | Person-years of exposure | Incidence rate, per 1000 person-years (95% CI) | Crude HR | Adjusted HR* (95% CI) |
|---|---|---|---|---|---|
| Sulfonylurea, n = 762 | 40 | 503 | 79.5 (56.8–108.3) | 1.00 | 1.00 (reference) |
| Metformin, n = 4927 | 455 | 3633 | 125.2 (114.0–137.3) | 1.60 | 1.55 (1.09–2.20) |
| Duration of use† | |||||
| < 90 d | |||||
| Sulfonylurea | 10 | 143 | 69.9 (33.5–128.6) | 1.00 | 1.00 (reference) |
| Metformin | 124 | 984 | 126.0 (104.8–150.2) | 1.80 | 1.73 (0.90–3.34) |
| 90–180 d | |||||
| Sulfonylurea | 6 | 88 | 68.2 (25.0–148.4) | 1.00 | 1.00 (reference) |
| Metformin | 99 | 619 | 159.9 (130.0–194.7) | 2.34 | 2.30 (1.00–5.29) |
| > 180 d | |||||
| Sulfonylurea | 24 | 272 | 88.2 (56.5–131.3) | 1.00 | 1.00 (reference) |
| Metformin | 232 | 2030 | 114.3 (100.0–130.0) | 1.32 | 1.29 (0.83–2.01) |
Note: CI = confidence interval, HR = hazard ratio, TSH = thyroid-stimulating hormone.
↵* Adjusted for age, sex, year of cohort entry, body mass index, smoking, excessive alcohol use (i.e., alcohol-related disorders such as alcoholism, alcoholic cirrhosis, alcoholic hepatitis and hepatic failure), hemoglobin A1C, duration of diabetes, and use of lithium, amiodarone and glucocorticoids.
↵† Hazard ratios were estimated using time-dependent Cox proportional hazards models.