Table 3.
Risk of specific cancer in patients using insulin glargine or other insulin analogues in comparison with those using human insulin (as-treated analysis)
| Full modela | Insulin glargine | Other insulin analogues | Human insulin | ||||||
|---|---|---|---|---|---|---|---|---|---|
| IR | n | HR | 95% CI | IR | n | HR | 95% CI | IR | |
| Colon cancer | |||||||||
| Full | 1.29 | 18 | 0.55 | 0.39, 0.76 | 2.02 | 62 | 1.07 | 0.93, 1.25 | 1.90 |
| Full model, adjusted for use of OGLD (time-dependent) | |||||||||
| Biguanide | 0.72 | 0.63, 0.85 | 1.06 | 0.91, 1.23 | |||||
| SU | 0.72 | 0.62, 0.84 | 1.08 | 0.93, 1.26 | |||||
| Other OGLD | 0.73 | 0.63, 0.85 | 1.07 | 0.91, 1.26 | |||||
| Full model + average DDD | 0.55 | 0.40, 0.76 | 0.97 | 0.81, 1.15 | |||||
| Full model, stratified for dose of first insulin prescription | |||||||||
| <Median | 0 | – | 0 | – | |||||
| Median | 16 | 0.30 | 0.17, 0.54 | 44 | 0.89 | 0.70, 1.14 | |||
| >Median | 2 | – | 18 | 0.77 | 0.59, 1.00 | ||||
| Full model including a latency time of 1 yearb | 0.86 | 12 | 0.61 | 0.40, 0.91 | 1.14 | 35 | 1.20 | 0.97, 1.48 | 1.58 |
| Bladder cancer | |||||||||
| Full | 0.79 | 11 | 1.89 | 0.69, 3.21 | 0.91 | 28 | 0.48 | 0.34, 0.69 | 1.06 |
| Full model, adjusted for use of OGLD (time-dependent) | |||||||||
| Biguanide | 0.83 | 0.68, 1.01 | 0.80 | 0.65, 0.98 | |||||
| SU | 0.84 | 0.69, 1.02 | 0.80 | 0.66, 0.98 | |||||
| Other OGLD | 0.83 | 0.68, 1.01 | 0.80 | 0.66, 0.98 | |||||
| Full model + average DDD | 1.38 | 0.70, 2.70 | 0.48 | 0.32, 0.70 | |||||
| Full model, stratified for dose of first insulin prescription | |||||||||
| <Median | 0 | – | 1 | – | |||||
| Median | 8 | 2.27 | 1.24, 4.15 | 16 | 0.56 | 0.39, 0.79 | |||
| >Median | 3 | – | 11 | 0.79 | 0.60, 1.04 | ||||
| Full model including a latency time of 1 yearb | 0.50 | 7 | 1.09 | 0.37, 3.24 | 0.61 | 19 | 0.66 | 0.44, 0.99 | 0.80 |
| Respiratory tract cancer | |||||||||
| Full | 1.64 | 23 | 1.03 | 0.84, 1.24 | 1.89 | 58 | 0.64 | 0.54, 0.77 | 1.90 |
| Full model, adjusted for use of OGLD (time-dependent) | |||||||||
| Biguanide | 1.01 | 0.82, 1.24 | 0.87 | 0.78, 0.96 | |||||
| SU | 0.97 | 0.79, 1.20 | 0.87 | 0.78, 0.96 | |||||
| Other OGLD | 1.02 | 0.82, 1.25 | 0.86 | 0.78, 0.95 | |||||
| Full model + average DDD | 0.76 | 0.61, 0.96 | 0.64 | 0.54, 0.77 | |||||
| Full model, stratified for dose of first insulin prescription | |||||||||
| <Median | 0 | – | 1 | – | |||||
| Median | 15 | 1.09 | 0.57, 2.07 | 34 | 0.46 | 0.30, 0.71 | |||
| >Median | 8 | 1.14 | 0.79, 1.63 | 23 | 0.93 | 0.80, 1.08 | |||
| Full model including a latency time of 1 yearb | 1.07 | 15 | 1.23 | 0.94, 1.62 | 1.17 | 36 | 0.91 | 0.73, 1.12 | 1.32 |
| Prostate cancer | |||||||||
| Full | 0.99 | 7 | 2.76 | 1.32, 5.80 | 1.26 | 19 | 0.83 | 0.70, 1.03 | 1.55 |
| Full model, adjusted for use of OGLD (time-dependent) | |||||||||
| Biguanide | 2.74 | 1.29, 5.80 | 0.84 | 0.70, 1.03 | |||||
| SU | 3.12 | 1.35, 7.19 | 0.83 | 0.70, 1.03 | |||||
| Other OGLD | 2.72 | 1.28, 5.79 | 0.85 | 0.73, 1.09 | |||||
| Full model + average DDD | 1.01 | 0.62, 1.73 | 0.99 | 0.95, 1.04 | |||||
| Full model, stratified for dose of first insulin prescription | |||||||||
| <Median | 0 | – | 0 | – | |||||
| Median | 5 | 2.21 | 0.92, 5.34 | 11 | 0.83 | 0.53, 1.39 | |||
| >Median | 2 | – | 8 | 0.87 | 0.67, 1.16 | ||||
| Full model including a latency time of 1 yearb | 0.71 | 5 | 2.19 | 1.03, 4.66 | 0.79 | 12 | 0.84 | 0.68, 1.43 | 1.15 |
| Breast cancer | |||||||||
| Full | 4.06 | 28 | 1.58 | 1.22, 2.05 | 3.08 | 48 | 0.95 | 0.83, 1.08 | 2.81 |
| Full model, adjusted for use of OGLD (time-dependent) | |||||||||
| Biguanide | 1.58 | 1.22, 2.04 | 0.94 | 0.81, 1.08 | |||||
| SU | 1.67 | 1.28, 2.19 | 0.94 | 0.82, 1.08 | |||||
| Other OGLD | 1.52 | 1.16, 1.98 | 1.03 | 0.89, 1.20 | |||||
| Full model + average DDD | 1.62 | 1.24, 2.12 | 0.90 | 0.80, 1.02 | |||||
| Full model, stratified for dose of first insulin prescription | |||||||||
| <Median | 2 | – | 3 | – | |||||
| Median | 15 | 1.22 | 0.91, 1.64 | 29 | 0.90 | 0.70, 1.15 | |||
| >Median | 11 | 2.81 | 1.23, 6.44 | 16 | 0.10 | 0.02, 0.47 | |||
| Full model including a latency time of 1 yearb | 1.60 | 11 | 1.65 | 1.10, 2.47 | 1.99 | 31 | 0.99 | 0.81, 1.20 | 2.28 |
aIn the full model, adjustments were made for age at first insulin prescription, sex, calendar time, number of unique drugs used in the year before start of insulin and number of hospitalisations in the year before start of insulin. Days of prior OGLD use, number of days of OGLD use as of January 1998. Furthermore, when the insulin of interest was insulin glargine, adjustments were made for the use of other insulin analogues as time-dependent variables; when the insulin of interest were other insulin analogues, adjustments were made for the use of insulin glargine
bModel included a 1 year latency period: exposure was cumulated up till one year prior to the date of cancer diagnosis
IR, incidence rate; n, number of events; SU, sulfonylurea derivative