Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.
OBJECTIVE
The aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin.


METHODS
We used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n = 36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n = 12,852 in whom 381 cancers occurred). Records from these cohorts were linked to cancer registry data up to the end of 2005. We used Cox proportional hazards models for survival analyses.


RESULTS
Those receiving any insulin glargine (n = 3,959) had the same incidence rate for all cancers as those not receiving insulin glargine (HR 1.02, 95% CI 0.77-1.36, p = 0.9 in the fixed cohort) The subset of patients using insulin glargine alone (n = 447) had a significantly higher incidence of all cancers than those using other insulins only (n = 32,295) (HR 1.55, 95% CI 1.01-2.37, p = 0.045), and those using insulin glargine with other insulins (n = 3,512) had a slightly lower incidence (HR 0.81, 95% CI 0.55-1.18, p = 0.26). There were important differences in baseline characteristics between these three groups, although the risk ratios were broadly unaltered on adjustment for these. Overall, there was no increase in breast cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79-2.83, though insulin glargine only users had a higher rate than those using non-glargine insulin only (HR 3.39, 95% CI 1.46-7.85, p = 0.004). Among type 2 diabetic incident insulin users, no significant difference between the three groups was observed with respect to all cancer or breast cancer. All the above HRs are adjusted for age, calendar time prior cancer and type of diabetes, as appropriate, and are stratified according to sex.


CONCLUSIONS
Overall, insulin glargine use was not associated with an increased risk of all cancers or site-specific cancers in Scotland over a 4 year time frame. Given the overall data, we consider the excess of cases of all cancers and breast cancer in the subgroup of insulin glargine only users to more likely reflect allocation bias rather than an effect of insulin glargine itself.
Colhoun
H M
HM
Biomedical Research Institute, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK. h.colhoun@cpse.dundee.ac.uk
D001943:Breast Neoplasms / Q000453:epidemiology / Q000401:mortality; D002874:Chromosome Mapping; D048909:Diabetes Complications / Q000453:epidemiology* / Q000401:mortality; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality; D011336:Probability; D012042:Registries; D012189:Retrospective Studies; D012606:Scotland / Q000453:epidemiology; D016019:Survival Analysis
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine