Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone
Interim report of a longitudinal cohort study
Article Figures & Tables
Tables
- Table 1
Demographics of the study cohort according to ever use of pioglitazone: the KPNC diabetes registry, 1997–2008
Ever use of pioglitazone* Never use of pioglitazone* N 30,173 162,926 Age (years) 40–49 8,612 (28.5) 36,452 (22.4) 50–59 9,945 (33.0) 41,962 (25.8) 60–69 7,799 (25.8) 42,691 (26.2) ≥70 3,817 (12.7) 41,821 (25.7) Sex (female) 14,157 (46.9) 75,686 (46.5) Race/ethnicity White 14,768 (48.9) 80,777 (49.6) Black 2,823 (9.4) 16,731 (10.3) Asian 3,834 (12.7) 18,877 (11.6) Hispanic 3,320 (11.0) 14,430 (8.9) Other 1,691 (5.6) 8,876 (5.4) Missing 3,737 (12.4) 23,235 (14.3) Current smoker 6,052 (20.1) 28,023 (17.2) Renal function Normal creatinine 23,174 (76.8) 125,879 (77.3) Elevated creatinine† 1248 (4.1) 13,993 (8.6) Missing 5,751 (19.1) 23,054 (14.2) Bladder condition‡ 3,686 (12.2) 25,581 (15.7) Congestive heart failure 969 (3.2) 11,038 (6.8) Income Low§ 14,413 (47.8) 82,270 (50.5) High 12,825 (42.5) 66,133 (40.6) Missing 2,935 (9.7) 14,523 (8.9) Baseline A1C (%) <7 4,873 (16.2) 46,407 (28.5) 7–7.9 5,455 (18.1) 31,517 (19.3) 8–8.9 3,921 (13.0) 17,060 (10.5) 9–9.9 2,979 (9.9) 11,524 (7.1) ≥10 7,330 (24.3) 28,017 (17.2) Missing 5,615 (18.6) 28,401 (17.4) Newly diagnosed with diabetes at the start of follow-up¶ 14,687 (48.7) 94,739 (58.1) Duration of diabetes (years) 0–5 17,363 (57.5) 102,916 (63.2) 5–9 2,983 (9.9) 9,671 (5.9) ≥10 2,956 (9.8) 17,432 (10.7) Missing 6,871 (22.8) 32,907 (20.2) Other cancer prior to baseline 1,186 (3.9) 8,762 (5.4) Other diabetes medications Other TZDs 2,754 (9.1) 2,470 (1.5) Metformin 24,797 (82.2) 70,956 (43.6) Sulfonylureas 26,311 (87.2) 95,429 (58.6) Other oral hypoglycemic drugs 1,482 (4.9) 1,865 (1.1) Insulin 13,123 (43.5) 41,337 (25.4) Pioglitazone use during follow-up Time since starting pioglitazone (months) 39.5 (1–102) N/A <18 7,245 (24.0) N/A 18–36 6,681 (22.1) N/A >36 16,247 (53.8) N/A Duration of therapy (months) 24.1 (1–102) N/A <12 7,332 (24.3) N/A 12–24 7,677 (25.4) N/A >24 15,164 (50.3) N/A Cumulative dose (mg) 17,670 (450–179,000) N/A 1–10,500 10,281 (34.1) N/A 10,501–28,000 9,667 (32.0) N/A >28,000 10,225 (33.9) N/A Data are n (%) or median (range) unless otherwise indicated. N/A, not applicable.
↵*All comparisons have P values <0.01 except female sex (P = 0.46).
↵†Creatinine ≥1.4 mg/dL for women and ≥1.5 mg/dL for men.
↵‡History of urinary tract infections, urolithiasis, incontinence, and other bladder or urethral conditions.
↵§Low income defined as median household income in census block below the cohort average ($59,000).
↵¶Includes newly diagnosed patients and patients who newly enrolled in KPNC with an existing diagnosis of diabetes.
- Table 2
Incidence rate and HR of bladder cancer with pioglitazone use: the KPNC diabetes registry, 1997–2008
Median (range) bladder cancer incidence rate (per 100,000 person-years) HR (95% CI) adjusted for age and sex Fully adjusted HR (95% CI)* Never use of pioglitazone 68.8 (64.1–73.6) Ref. Ref. Ever use of pioglitazone† 81.5 (64.7–98.4) 1.2 (0.9–1.5)‡ 1.2 (0.9–1.5) Time since starting pioglitazone (months)† <18 67.1 (41.8–92.4) 1.1 (0.8–1.6) 1.2 (0.8–1.7) 18–36 85.2 (51.8–118.6) 1.3 (0.9–2.0) 1.4 (0.9–2.1) >36 93.1 (63.5–122.7) 1.3 (0.9–1.8) 1.3 (0.9–1.8) Ptrend — 0.04 0.07 Duration of therapy (months)† <12 48.4 (29.0–67.8) 0.8 (0.5–1.2) 0.8 (0.6–1.3) 12–24 86.7 (52.0–121.4) 1.3 (0.9–2.0) 1.4 (0.9–2.1) >24 102.8 (71.7–133.8) 1.5 (1.1–2.0) 1.4 (1.03–2.0) Ptrend — 0.02 0.03 Cumulative dose (mg)† 1–10,500 59.7 (39.0–80.4) 1.0 (0.7–1.4) 1.0 (0.7–1.5) 10,501–28,000 76.8 (48.3–105.2) 1.1 (0.8–1.6) 1.2 (0.8–1.8) >2,8000 105.9 (68.0–143.8) 1.5 (1.1–2.2) 1.4 (0.96–2.1) Ptrend — 0.05 0.08 ↵*Includes all potential confounders listed in Table 1 in the statistical model.
↵†Never use of pioglitazone was the reference group for the calculation of the HR associated with ever use of pioglitazone and time, duration, and dose of pioglitazone use.
↵‡Also adjusted for use of other diabetes medications.