Endocrine Abstracts (2013) 32 P348 | DOI: 10.1530/endoabs.32.P348

Long-acting insulin analogs exposure and cancer specific mortality in patients with diabetes mellitus

Sorin Ioacara1, Cristian Guja1, Constantin Ionescu-Tirgoviste1, Simona Fica2, Sorina Martin2 & Michael Roden3


1‘I. Pavel’ Outpatient Clinic, Bucharest, Romania; 2‘Elias’ Hospital, Bucharest, Romania; 3Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany.


Aim: To test the hypothesis that exposure to insulin glargine might be associated with increased risk of cancer mortality compared with human basal insulin preparations.

Materials and methods: All consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001 and 12/31/2008 (n=79 869). Exclusion criteria were insulin treatment at screening (n=14 752), no insulin treatment until 12/31/2008 (n=55 795), <6 months of glucose-lowering treatment alone before insulin initiation (n=1154), insulin prescription before glargine became available (04/17/2003, n=1761), age <40 or ≥80 years at first insulin prescription (n=406), <6 months of insulin treatment following insulin initiation. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011, using data from National Institute of Statistics. Baseline was defined at 6 months after insulin initiation. Antidiabetic prescriptions were available. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Simultaneously use of cumulative exposure and ever exposed term of the available treatment options, a ‘fixed’ cohort, cumulative exposure limited to that attained one year prior to death (minimizing the reverse causation), and a propensity score analysis completed the evaluation.

Results: Mean baseline age was 62±9 years, and follow-up 4.7±1.9 years (23 179 person-years). Glargine cumulative dose exposure significantly lowered cancer mortality risk, subhazard ratio (SHR) 0.94 (95% CI 0.89–0.99, P=0.033). Cumulative exposure limited to that attained 1 year prior to death showed a glargine cumulative exposure time SHR 0.94 (95% CI 0.89–0.99, P=0.018) and cumulative dose SHR 0.92 (95% CI 0.86–0.98, P=0.014). Glargine use was associated with cumulative exposure time and cumulative dose that were significant predictors for lower pancreatic and breast cancer mortality, but with no impact on lung, colorectal, female genital, liver, and urinary tract cancer deaths.

Conclusions: The cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. No glargine associated ‘harm’ was found even after additional ‘fixed’ cohort or propensity score analyses were performed.

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