Association of metformin dosage at points 3, 12 and 24 months after first prescription with incidence of total joint replacement
| Variable | Adjusted HR* (95% CI) | ||
|---|---|---|---|
| TKR or THR | TKR | THR | |
| 3 months after first prescription | |||
| Ordinal model | |||
| Patients who did not use metformin (n = 20 347) | Ref. | Ref. | Ref. |
| Patients on < 1.0 g/d metformin (n = 14 621) | 0.69 (0.59–0.81) | 0.70 (0.59–0.83) | 0.63 (0.42–0.96) |
| Patients on ≥ 1.0 g/d metformin (n = 5726) | 0.75 (0.60–0.94) | 0.79 (0.61–1.00) | 0.56 (0.29–1.07) |
| p for trend | < 0.001 | 0.003 | 0.024 |
| 12 months after first prescription | |||
| Ordinal model | |||
| Patients who did not use metformin (n = 18 103) | Ref. | Ref. | Ref. |
| Patients on < 1.0 g/d metformin (n = 16 143) | 0.82 (0.70–0.97) | 0.85 (0.71–1.01) | 0.67 (0.41–1.07) |
| Patients on < 1.0 g/d metformin ≥ 1.0 g per day (n = 3079) | 0.75 (0.54–1.04) | 0.79 (0.56–1.12) | 0.50 (0.19–1.33) |
| p for trend | 0.014 | 0.054 | 0.060 |
| Adherence model | |||
| Patients who did not use metformin (n = 18 103) | Ref. | Ref. | Ref. |
| Previous users of metformin (n = 5241) | 0.83 (0.52–1.35) | 0.78 (0.46–1.32) | 1.34 (0.42–4.31) |
| Continuing users of metformin (n = 13 981) | 0.72 (0.48–1.09) | 0.70 (0.45–1.10) | 0.93 (0.28–3.05) |
| 24 months after first prescription | |||
| Ordinal model | |||
| Patients who did not use metformin (n = 14 924) | Ref. | Ref. | Ref. |
| Patients on < 1.0 g/d metformin (n = 14 149) | 0.81 (0.67–0.98) | 0.81 (0.66–0.99) | 0.80 (0.48–1.35) |
| Patients on ≥ 1.0 g/d metformin (n = 2189) | 0.77 (0.52–1.13) | 0.81 (0.54–1.21) | 0.55 (0.16–1.91) |
| p for trend | 0.031 | 0.062 | 0.273 |
| Adherence model | |||
| Patients who did not use metformin (n = 14 924) | Ref. | Ref. | Ref. |
| Previous users of metformin (n = 5063) | 0.88 (0.71–1.09) | 0.86 (0.69–1.08) | 1.01 (0.57–1.82) |
| Continuing users of metformin (n = 11 275) | 0.72 (0.57–0.92) | 0.75 (0.58–0.96) | 0.52 (0.24–1.12) |
Note: CI = confidence interval, HR = hazard ratio, Ref. = reference category, THR = total hip replacement, TKR = total knee replacement.
↵* Unless indicated otherwise. The covariates include baseline demographic variables (including sex, age, urbanization, insurance type), and time-dependent covariates (including score of adapted Diabetes Complication Severity Index, comorbidities, medications for pain management, other oral antihyperglycemic agents and insulin use). The average daily dosage was calculated at 3, 12 and 24 months after the first metformin prescription. All individuals were at risk and followed after the time points of interest. We categorized participants treated with metformin as either continuing users (defined as participants who used metformin, including within 9 mo before index date), and previous users (defined as participants who had used metformin, but not within 9 mo before index date) at 12 and 24 months after first prescription of metformin.