Glucose lowering therapies and cancer specific mortality in adult insulin-treated diabetes
S. Ioacara1, C. Guja1, C. Ionescu-Tirgoviste1, S. Fica2, S. Martin2, S. Sabau3 & C. Tiu4
Aim: Following the general concern regarding the association between various diabetes treatments and cancer risk, the present study evaluated the cancer specific mortality in adult insulin-treated diabetes patients.
Materials and methods: All diabetes patients residing in a major urban area, aged over 40 years and receiving insulin treatment were included at the moment of their first diabetes outpatient visit from 01/01/2001 to 12/31/2008. A total of 11366 subjects (46.5% males) were followed-up for death of any cause until 12/31/2010 by crosslinking with the National Institute of Statistics mortality database, with a virtually 100% cover-up. Mortality data for the general population was obtained from the same source. Death related data was based on death certificate. Antidiabetic prescriptions were available from local pharmacies or prescribing institutions. Subjects with <6 months of follow-up were excluded (avoiding protopathic bias). Age and sex adjusted time-dependent Cox proportional hazard analysis (1 month update of treatment modalities) was performed.
Results: Mean age at baseline was 59.8±10.7 years, mean follow-up period 6.75±2.98 years (76697.9 person-years). Overall, unadjusted all-cause mortality was 49.7/1000 person-years (3811 deaths); cancer mortality was 6.9/1000 person-years (531 deaths). The major types of cancers were: pulmonary (n=94, 17.7%), pancreatic (n=67, 12.6%), liver (n=64, 12.1%), colorectal (n=60, 11.3%), breast (n=55, 10.4%) and stomach (n=25, 4.7%). Adjusted hazard ratios for cancer mortality (CI95%) were: biguanides 0.49 (0.350.68, P<0.001), sulfonylurea 0.9 (0.641.26, P=0.54), human rapid insulin 1.17 (0.961.41, P=0.11), rapid analogs 0.74 (0.461.22, P=0.24), human premixed insulin 0.85 (0.591.24, P<0.4), premixed analogs 0.91 (0.591.38, P<0.64), human intermediate insulin 0.82 (0.531.26, P=0.36), glargine 1.05 (0.641.74, P=0.84), and detemir 1.54 (0.753.15, P=0.24).
Conclusions: Biguanides are the only diabetes treatment choice associated with an independent, statistical significant (protective) effect on cancer mortality. Of interest, exposure to long acting analogues was not associated with increased cancer mortality in insulin treated subjects.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.