Introduction
Methods
Setting
Study population
Exposure
Outcome
Covariables
Statistical analysis
Results
Setting and characteristics
Variable | Insulin glargine (n = 3,789) | Other insulin analogues (n = 6,032) | Human insulin (n = 9,516) |
---|---|---|---|
Age at first prescription of insulin in yearsa
| 63.1 ± 13.7 | 61.8 ± 13.9 | 65.0 ± 13.5 |
Sex, n (%)b
| |||
Male | 1,901 (50.2) | 2,931 (48.6) | 4,423 (46.5) |
Female | 1,888 (49.8) | 3,101 (51.4) | 5,093 (53.5) |
Total number of unique other drugs used in the year before first prescription of insulinc
| |||
Mean ± SD | 8.8 ± 5.6 | 8.9 ± 6.0 | 9.0 ± 6.2 |
Median (IQR) | 8 (5–8) | 8 (5–8) | 8 (5–8) |
Total number of hospitalisations in the year before first prescription of insulinc
| |||
Mean ± SD | 0.5 (2.1) | 0.6 (1.1) | 0.6 (1.1) |
Median (IQR) | 0 (0–1) | 0 (0–1) | 0 (0–1) |
Number of days of OGLD use in the year before first prescription of insulin, median (IQR)a
| 324 (280–350) | 320 (235–348) | 324 (276–349) |
Number of days of OGLD use before first prescription of insulin as of January 1998, median (IQR)a
| 1,567 (548–2,474) | 1,190 (275–2,134) | 1,154 (383–1,090) |
Duration of follow-up since first insulin prescription in daysa
| |||
Mean ± SD | 803 ± 587 | 1,186 ± 823 | 1,381 ± 924 |
Median (IQR) | 659 (307–1,176) | 813 (344–1,489) | 1,629 (755–2,350) |
Average daily dose of the first insulin prescription (U)a
| |||
Mean ± SD | 21.7 ± 13.5 | 28.1 ± 46.6 | 26.0 ± 19.8 |
Median (IQR) | 16.7 (16.7–16.7) | 16.7 (16.7–33.3) | 16.7 (16.7–33.3) |
Average daily dose over all insulin prescriptions in U since first prescriptiona
| |||
Mean ± SD | 44.1 ± 63.4 | 15.4 ± 44.5 | 55.6 ± 112.0 |
Median (IQR) | 34.0 (22.0–50.0) | 15.0 (14.0–18.0) | 46.0 (26.0–64.0) |
Types of insulin, first prescription, n (%) | |||
Fast-acting | NA | 1,899 (31.5) | 1,346 (14.1) |
Intermediate fast-acting | NA | 11 (0.2) | 4,479 (47.1) |
Intermediate and fast-acting | NA | 3,065 (50.8) | 3,691 (38.8) |
Long-acting | 3,789 (100.0) | 1,056 (17.5) | NA |
As-treated analyses
Covariablesa included in the model | Insulin glargine | Other insulin analogues | ||
---|---|---|---|---|
HR | 95% CI | HR | 95% CI | |
None | 0.71 | 0.67, 0.75 | 0.79 | 0.76, 0.81 |
Stratified for dose of first insulin prescription | ||||
<Median | 0.71 | 0.56, 0.89 | 0.87 | 0.76, 0.98 |
Median | 0.71 | 0.66, 0.77 | 0.75 | 0.72, 0.79 |
>Median | 0.68 | 0.61, 0.76 | 0.86 | 0.82, 0.91 |
Age, sex | 0.72 | 0.68, 0.76 | 0.80 | 0.77, 0.82 |
Age, sex, calendar time, hospitalisations, unique drugs | 0.75 | 0.71, 0.79 | 0.84 | 0.81, 0.87 |
Full model: age, sex, calendar time, hospitalisations, unique drugs, use of other insulin | 0.75 | 0.71, 0.80 | 0.85 | 0.82, 0.89 |
Full model, adjusted for time since cessationb
| 0.72 | 0.67, 0.76 | 0.82 | 0.79, 0.86 |
Full model, adjusted for days of prior OGLD use | ||||
<1 year OGLD use | 0.77 | 0.65, 0.90 | 0.81 | 0.74, 0.89 |
≥1 year OGLD use | 0.79 | 0.74, 0.84 | 0.93 | 0.88, 0.98 |
Full model, adjusted for use of OGLD (time-dependent) | ||||
Biguanide | 0.75 | 0.71, 0.80 | 0.85 | 0.82, 0.89 |
SU | 0.76 | 0.71, 0.80 | 0.85 | 0.81, 0.88 |
Other OGLD | 0.75 | 0.71, 0.80 | 0.85 | 0.82, 0.89 |
Full model, adjusted for average DDD | 0.75 | 0.71, 0.80 | 0.85 | 0.82, 0.89 |
Full model, stratified for dose of first insulin prescription | ||||
<Median | 0.70 | 0.54, 0.89 | 0.89 | 0.74, 1.08 |
Median | 0.79 | 0.73, 0.85 | 0.81 | 0.76, 0.85 |
>Median | 0.72 | 0.64, 0.80 | 0.92 | 0.86, 0.98 |
Full model including a latency time of 1 yearc
| 0.76 | 0.71, 0.81 | 0.88 | 0.84, 0.93 |
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 |