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Original Research

New Users of Metformin Are at Low Risk of Incident Cancer

A cohort study among people with type 2 diabetes

  1. Gillian Libby, MSC1,
  2. Louise A. Donnelly1,
  3. Peter T. Donnan, PHD1,
  4. Dario R. Alessi, PHD2,
  5. Andrew D. Morris, FRCP3 and
  6. Josie M.M. Evans, PHD1
  1. 1Division of Clinical and Population Sciences and Education, University of Dundee, Dundee, U.K.;
  2. 2School of Life Sciences, University of Dundee, Dundee, U.K.;
  3. 3Diabetes Research Centre, University of Dundee, Dundee, U.K.
  1. Corresponding author: Josie M.M. Evans, j.m.m.stansfield{at}cpse.dundee.ac.uk.
Diabetes Care 2009 Sep; 32(9): 1620-1625. https://doi.org/10.2337/dc08-2175
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    Figure 1

    Flowchart showing how metformin users and comparators were selected for the study.

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    Figure 2

    Kaplan-Meier plot with 95% CIs showing time to cancer among metformin users and comparators.

Tables

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  • Table 1

    Baseline characteristics and results of Cox regression analysis for incidence of cancer among metformin users and comparators

    Metformin usersComparatorsDiagnosed cancerUnadjustedAdjusted*
    Comparators4,085—4741.001.00
    Metformin users—4,0852970.46 (0.40–0.53)0.63 (0.53–0.75)
    Sex
        Female1,848 (45.9)1,875 (45.2)3151.001.00
        Male2,237 (54.1)2,210 (54.8)4561.26 (1.09–1.45)1.37 (1.18–1.59)
    Age (years)
        35–551,001 (24.5)533 (13.1)511.001.00
        56–63964 (23.6)647 (15.8)1382.72 (1.97–3.75)2.66 (1.92–3.68)
        64–69865 (21.2)691 (16.9)1603.40 (2.48–4.67)3.13 (2.27–4.32)
        70–76781 (19.1)939 (23.0)2054.61 (3.39–6.28)4.09 (2.98–5.61)
        77–100474 (11.6)1,275 (31.2)2175.95 (4.37–8.12)4.86 (3.51–6.73)
    Smoking status
        Current577 (14.1)558 (13.7)1091.001.00
        Ex-smoker1,015 (24.9)866 (21.2)1770.99 (0.78–1.26)0.77 (0.60–0.98)
        Never1,637 (40.1)1,411 (34.5)2710.87 (0.69–1.09)0.75 (0.60–0.94)
        Not known856 (21.0)1,250 (30.6)2141.19 (0.94–1.51)0.91 (0.72–1.16)
    Carstairs deprivation category
        1 (least deprived)224 (5.5)206 (5.0)461.001.00
        2805 (19.7)902 (22.1)1620.75 (0.56–1.01)0.74 (0.55–0.99)
        31,129 (27.6)1,171 (28.7)2230.80 (0.61–1.07)0.82 (0.62–1.09)
        4458 (11.2)488 (12.0)990.78 (0.56–1.08)0.81 (0.58–1.12)
        5521 (12.8)457 (11.2)770.66 (0.47–0.92)0.69 (0.49–0.97)
        6603 (14.8)579 (14.2)1060.71 (0.52–0.98)0.79 (0.58–1.09)
        7 (most deprived)345 (8.5)282 (6.9)580.72 (0.50–1.04)0.83 (0.58–1.19)
    BMI30.7 ± 3.528.6 ± 3.1—0.93 (0.91–0.95)0.98 (0.96–1.00)
    A1C (%)7.9 ± 1.07.2 ± 1.2—0.77 (0.72–0.82)0.91 (0.84–0.98)
    Insulin use
        No use3,833 (93.8)3,512 (86.0)6961.001.00
        Use within 1 year252 (6.2)573 (14.0)750.99 (0.85–1.15)1.13 (0.97–1.33)
    Sulphonylurea use
        No use2,196 (53.8)1,996 (73.3)4831.001.00
        Use within 3 months1,889 (46.2)1,089 (26.7)2881.00 (0.78–1.28)1.12 (0.87–1.47)
    • Data are n, n (%), means ± SD, or HR (95% CI).

    • ↵*Adjusted for all covariates.

  • Table 2

    Unadjusted and adjusted HRs for secondary outcomes with adjusted HRs for incidence of cancer stratified by maximum prescribed dose and duration of follow-up with comparators as the reference category

    n (%)UnadjustedAdjusted*
    Incidence of bowel cancer
        Comparators76 (1.9)1.001.00
        Users40 (1.0)0.41 (0.28–0.61)0.60 (0.38–0.94)
    Incidence of lung cancer
        Comparators58 (1.4)1.001.00
        Users35 (0.9)0.49 (0.32–0.74)0.70 (0.43–1.15)
    Incidence of breast cancer in women
        Comparators41 (2.2)1.001.00
        Users24 (1.3)0.44 (0.26–0.73)0.60 (0.32–1.10)
    Overall mortality
        Comparators1,422 (34.8)1.001.00
        Users609 (14.9)0.32 (0.29–0.35)0.42 (0.38–0.47)
    Mortality from cancer
        Comparators248 (6.1)1.001.00
        Users123 (3.0)0.48 (0.39–0.60)0.63 (0.49–0.81)
    Incidence of cancer<2 years follow-up*2–4 years follow-up*>4 years follow-up*
        Maximum prescribed dose during follow-up (n)
    Low (1,017)3.15 (1.92–5.18)0.99 (0.44–2.25)0.16 (0.06–0.44)
    Medium (2,090)1.94 (1.20–3.13)0.51 (0.31–0.82)0.40 (0.27–0.60)
    High (978)2.76 (0.56–13.45)0.28 (0.12–0.70)0.15 (0.09–0.25)
    • Data are HR (95% CI) unless otherwise indicated.

    • ↵*Adjusted for age, sex, smoking, deprivation, BMI, A1C, insulin use, and sulphonylurea use.

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New Users of Metformin Are at Low Risk of Incident Cancer
Gillian Libby, Louise A. Donnelly, Peter T. Donnan, Dario R. Alessi, Andrew D. Morris, Josie M.M. Evans
Diabetes Care Sep 2009, 32 (9) 1620-1625; DOI: 10.2337/dc08-2175

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New Users of Metformin Are at Low Risk of Incident Cancer
Gillian Libby, Louise A. Donnelly, Peter T. Donnan, Dario R. Alessi, Andrew D. Morris, Josie M.M. Evans
Diabetes Care Sep 2009, 32 (9) 1620-1625; DOI: 10.2337/dc08-2175
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