Table 1.
Bladder Cancer Risk Related to Pioglitazone Use in Patients with DM Compared Globally and Regionally from OB Studies.
| Global | Sub-regional | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Outcomea | OR (95% CI) | P-Value | American plus Asian Regions | European Region | |||||
| Outcomea | OR (95% CI) | P-Value | Outcomea | OR (95% CI) | P-Value | ||||
| Study type | |||||||||
| Cohort | + | 1.14 (1.05, 1.24) | 0.001 | — | 1.08 (0.94, 1.24) | 0.26 | + | 1.18 (1.07, 1.30) | 0.001 |
| Case-control | — | 1.21 (0.97, 1.52) | 0.10 | — | 1.10 (0.85, 1.41) | 0.47 | + | 1.83 (1.10, 3.05) | 0.02 |
| Adjustment factors | |||||||||
| Age and sex | |||||||||
| Adjusted | + | 1.15 (1.06, 1.24) | 0.001 | — | 1.07 (0.94, 1.21) | 0.30 | + | 1.24 (1.06, 1.46) | 0.009 |
| Unadjusted | — | 1.30 (0.86, 1.96) | 0.22 | — | 1.75 (0.92, 3.34) | 0.09 | — | 1.05 (0.61, 1.80) | 0.86 |
| Smoking | |||||||||
| Adjusted | + | 1.18 (1.05, 1.32) | 0.006 | — | 1.04 (0.89, 1.21) | 0.64 | + | 1.38 (1.16, 1.65) | < 0.001 |
| Unadjusted | + | 1.13 (1.03, 1.25) | 0.01 | — | 1.16 (0.96, 1.39) | 0.13 | — | 1.12 (1.00, 1.26) | 0.052 |
| Use of other medications | |||||||||
| Adjusted | + | 1.11 (1.02, 1.21) | 0.02 | — | 1.05 (0.92, 1.20) | 0.45 | + | 1.15 (1.03, 1.29) | 0.01 |
| Unadjusted | + | 1.33 (1.12, 1.57) | 0.001 | — | 1.28 (0.95, 1.72) | 0.11 | + | 1.35 (1.10, 1.65) | 0.004 |
| Intervention measures | |||||||||
| Treatment duration, mo | |||||||||
| < 12 | — | 1.09 (0.95, 1.24) | 0.21 | — | 1.05 (0.76, 1.45) | 0.78 | — | 1.08 (0.87, 1.34) | 0.49 |
| 12–24 | + | 1.29 (1.09, 1.53) | 0.003 | — | 1.20 (0.94, 1.53) | 0.14 | + | 1.38 (1.10, 1.74) | 0.006 |
| > 24 | + | 1.50 (1.18, 1.91) | 0.001 | — | 1.50 (0.79, 2.82) | 0.21 | + | 1.52 (1.26, 1.85) | < 0.001 |
| Cumulative dose, mg | |||||||||
| 1–10500 | — | 1.12 (0.96, 1.30) | 0.17 | — | 0.96 (0.75, 1.24) | 0.78 | + | 1.22 (1.00, 1.49) | 0.048 |
| 10501–28000 | — | 1.13 (0.95, 1.35) | 0.16 | — | 0.87 (0.65, 1.18) | 0.37 | + | 1.29 (1.04, 1.60) | 0.02 |
| > 28000 | + | 1.45 (1.21, 1.74) | < 0.001 | — | 1.23 (0.96, 1.57) | 0.10 | + | 1.80 (1.37, 2.37) | < 0.001 |
| Comparator agents | |||||||||
| Agents use in control group | |||||||||
| Specific | + | 1.16 (1.07, 1.26) | < 0.001 | — | 1.11 (0.97, 1.26) | 0.12 | + | 1.24 (1.05, 1.47) | 0.01 |
| Non-specific | — | 1.02 (0.79, 1.33) | 0.86 | — | 0.92 (0.63, 1.34) | 0.66 | — | 1.14 (0.79, 1.65) | 0.49 |
| Follow-up Duration | |||||||||
| Mean period of follow-up, y | |||||||||
| Lower tertile, < 3.6 | — | 1.11 (0.99, 1.24) | 0.08 | — | 0.92 (0.63, 1.34) | 0.66 | — | 1.11 (0.92, 1.35) | 0.28 |
| Middle tertile, 3.6–4.8 | + | 1.30 (1.06, 1.60) | 0.013 | — | 1.62 (0.92, 2.86) | 0.10 | + | 1.26 (1.01, 1.57) | 0.04 |
| Upper tertile, ≥ 4.8 | — | 1.15 (0.91, 1.47) | 0.25 | — | 1.03 (0.89, 1.20) | 0.68 | + | 1.47 (1.14, 1.91) | 0.003 |
| Study population | |||||||||
| Target disease | |||||||||
| T2DMb | + | 1.15 (1.04, 1.27) | 0.006 | — | 1.10 (0.93, 1.31) | 0.24 | + | 1.24 (1.05, 1.47) | 0.01 |
| DMc | + | 1.15 (1.02, 1.29) | 0.02 | — | 1.06 (0.89, 1.27) | 0.48 | + | 1.14 (0.79, 1.65) | 0.49 |
| Study population region | |||||||||
| America | — | 1.03 (0.88, 1.21) | 0.68 | NA | NA | NA | NA | NA | NA |
| Europe | +1 | 1.20 (1.08, 1.32) | < 0.001 | NA | NA | NA | NA | NA | NA |
| Asia | — | 1.16 (0.96, 1.40) | 0.12 | NA | NA | NA | NA | NA | NA |
Abbreviations: DM, diabetes mellitus; OB, observational studies; T2DM, type 2 diabetes; T1DM, type 1 diabetes; NA, not available.
aThe outcome includes statistical increased risk of bladder cancer ( + ) and non-association (-) related to pioglitazone use.
bWith T1DM excluded.
cWith T1DM included.