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Diabetes medications and cancer: A way out of uncertainty

      Compared with non-diabetic people, people with type 2 diabetes have an increased risk of developing a wide range of common tumors and also have a poorer prognosis [
      • Renehan A.
      • Smith U.
      • Kirkman M.S.
      Linking diabetes and cancer: a consensus on complexity.
      ]. Both obesity and the metabolic syndrome, two disorders strongly linked with and major risk factors for type 2 diabetes, are associated with an increased risk of malignant disease in both sexes (Giugliano et al., unpublished data [

      Giugliano D, Chiodini P, Colao A, Lenzi A, Esposito K. Metabolic syndrome and risk of cancer: a meta-analysis Diabetes Care; in press.

      ,
      • Renehan A.G.
      • Tyson M.
      • Egger M.
      • Heller R.F.
      • Zwahlen M.
      Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.
      ]). Although it has been shown since 2005 that diabetes is associated with an increased risk of colorectal cancer (30% increased risk) and pancreas cancer (82% increased risk) compared with the non-diabetic population [
      • Larsson S.C.
      • Orsini N.
      • Wolk A.
      Diabetes mellitus and risk of colorectal cancer: a meta-analysis.
      ,
      • Huxley R.
      • Ansary-Moghaddam A.
      • Berrington de González A.
      • Barzi F.
      • Woodward M.
      Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies.
      ], this relationship attracted relatively little attention among diabetes researchers and health care providers, whose focus has been on the dominant role of cardiovascular disease. Ironically, the awakening of the clinical relevance of the link between diabetes and cancer was generated by safety concerns associated with the use of some diabetes medications, in particular in 2009 with the publication of a series of observational reports suggesting an association between insulin glargine and a possible increase in tumor risk [
      • Hemkens L.G.
      • Grouven U.
      • Bender R.
      • Günster C.
      • Gutschmidt S.
      • Selke G.W.
      • et al.
      Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study.
      ,
      • Currie C.J.
      • Poole C.D.
      • Gale E.A.
      The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.
      ,
      • Colhoun H.M.
      Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.
      ,
      • Jonasson J.M.
      • Ljung R.
      • Talbäck M.
      • Haglund B.
      • Gudbjörnsdòttir S.
      • Steineck G.
      Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden.
      ]. However these reports stimulated considerable debate among diabetes clinicians, oncologists, and epidemiologists, leading to the issuing of a consensus report from the American Cancer Society and the American Diabetes Association [
      • Giovannucci E.
      • Harlan D.M.
      • Archer M.C.
      • Bergenstal R.M.
      • Gapstur S.M.
      • Habel L.A.
      • et al.
      Diabetes and cancer: a consensus report.
      ]. A number of epidemiological studies and meta-analyses have tried to shed more light on this topic, with conflicting results. Large population-based studies failed to confirm an association between insulin glargine and malignancy risk in general [

      US Food and Drug Administration: FDA Drug Safety Communication: update to ongoing safety review of Lantus (insulin glargine) and possible risk of cancer. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm239376.htm [accessed 19.03.12].

      ]. On the other hand, several analyses were unable to rule out the possibility of an increased risk of breast cancer among women treated with glargine, in comparison with users of human insulin [
      • Suissa S.
      • Azoulay L.
      • Dell’Aniello S.
      • Evans M.
      • Vora J.
      • Pollak M.
      Long-term effects of insulin glargine on the risk of breast cancer.
      ,
      • Ruiter R.
      • Visser L.E.
      • van Herk-Sukel M.P.
      • Coebergh J.W.
      • Haak H.R.
      • Geelhoed-Duijvestijn P.H.
      • et al.
      Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.
      ].

      Keywords

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      References

        • Renehan A.
        • Smith U.
        • Kirkman M.S.
        Linking diabetes and cancer: a consensus on complexity.
        Lancet. 2010; 375: 2201-2202
      1. Giugliano D, Chiodini P, Colao A, Lenzi A, Esposito K. Metabolic syndrome and risk of cancer: a meta-analysis Diabetes Care; in press.

        • Renehan A.G.
        • Tyson M.
        • Egger M.
        • Heller R.F.
        • Zwahlen M.
        Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.
        Lancet. 2008; 371: 569-578
        • Larsson S.C.
        • Orsini N.
        • Wolk A.
        Diabetes mellitus and risk of colorectal cancer: a meta-analysis.
        J Natl Cancer Inst. 2005; 97: 1679-1687
        • Huxley R.
        • Ansary-Moghaddam A.
        • Berrington de González A.
        • Barzi F.
        • Woodward M.
        Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies.
        Br J Cancer. 2005; 92: 2076-2083
        • Hemkens L.G.
        • Grouven U.
        • Bender R.
        • Günster C.
        • Gutschmidt S.
        • Selke G.W.
        • et al.
        Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study.
        Diabetologia. 2009; 52: 1732-1744
        • Currie C.J.
        • Poole C.D.
        • Gale E.A.
        The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.
        Diabetologia. 2009; 52: 1766-1777
        • Colhoun H.M.
        Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.
        Diabetologia. 2009; 52: 1755-1765
        • Jonasson J.M.
        • Ljung R.
        • Talbäck M.
        • Haglund B.
        • Gudbjörnsdòttir S.
        • Steineck G.
        Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden.
        Diabetologia. 2009; 52: 1745-1754
        • Giovannucci E.
        • Harlan D.M.
        • Archer M.C.
        • Bergenstal R.M.
        • Gapstur S.M.
        • Habel L.A.
        • et al.
        Diabetes and cancer: a consensus report.
        Diabetes Care. 2010; 33: 1674-1685
      2. US Food and Drug Administration: FDA Drug Safety Communication: update to ongoing safety review of Lantus (insulin glargine) and possible risk of cancer. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm239376.htm [accessed 19.03.12].

        • Suissa S.
        • Azoulay L.
        • Dell’Aniello S.
        • Evans M.
        • Vora J.
        • Pollak M.
        Long-term effects of insulin glargine on the risk of breast cancer.
        Diabetologia. 2011; 54: 2254-2262
        • Ruiter R.
        • Visser L.E.
        • van Herk-Sukel M.P.
        • Coebergh J.W.
        • Haak H.R.
        • Geelhoed-Duijvestijn P.H.
        • et al.
        Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.
        Diabetologia. 2012; 55: 51-62
        • Jorgensen L.
        • Dideriksen L.
        • Drejen K.
        Carcinogenic effect of human insulin and B10Asp in female rats.
        Diabetologia. 1992; 35: A3
        • Mathieu C.
        • Gale E.A.
        Inhaled insulin: gone with the wind?.
        Diabetologia. 2008; 51: 1-5
        • von Kriegstein E.
        • von Kriegstein K.
        Inhaled insulin for diabetes mellitus.
        N Engl J Med. 2007; 356: 2106
        • Bowker S.L.
        • Yasui Y.
        • Veugelers P.
        • Johnson J.A.
        Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure.
        Diabetologia. 2010; 53: 1631-1637
        • Elashoff M.
        • Matveyenko A.V.
        • Gier B.
        • Elashoff R.
        • Butler P.C.
        Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies.
        Gastroenterology. 2011; 141: 150-156
      3. EASD commentary on the publication by Elashoff et al., published online in Gastroenterology, February 2011: increased incidence of pancreatitis and cancer among patients given glucagon like peptide-1-based therapy. Available from: http://www.easd.org/easdwebfiles/statements/Elashoff_Commentary.pdf [accessed 19.03.12].

      4. US Food and Drug Administration: FDA Drug Safety Communication: update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm259150.htm [accessed 19.03.12].

      5. European Medicines Agency recommends new contra-indications and warnings for pioglitazone to reduce small increased risk of bladder cancer. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2011/07/WC500109176.pdf [accessed 19.03.12].

        • Gerich J.E.
        • Bastien A.
        Development of the sodium-glucose co-transporter 2 inhibitor dapagliflozin for the treatment of patients with type 2 diabetes mellitus.
        Expert Rev Clin Pharmacol. 2011; 4: 669-683
        • Handelsman Y.
        • Jellinger P.S.
        Overcoming obstacles in risk factor management in type 2 diabetes mellitus.
        J Clin Hypertens (Greenwich). 2011; 13: 613-620
        • Nissen S.E.
        • Wolski K.
        Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.
        N Engl J Med. 2007; 356: 2457-2471
        • Fanning E.L.
        • Weissman P.N.
        • Menditto L.A.
        Clinical practice effect of rosiglitazone discontinuation on glycemic control.
        Endocr Pract. 2009; 15: 270-272
        • Giugliano D.
        • Esposito K.
        Clinical inertia as a clinical safeguard.
        JAMA. 2011; 305: 1591-1592
        • Stumvoll M.
        • Nawroth P.P.
        The insulin glargine dilemma: an opportunity for the diabetes community?.
        Diabetologia. 2009; 52: 1987-1989
        • Ceriello A.
        • Gallo M.
        • Armentano V.
        • Perriello G.
        • Gentile S.
        • De Micheli A.
        Personalizing treatment in type 2 diabetes: a SMBG inclusive innovative approach.
        Diabetes Technol Ther. 2012; 14: 373-378
        • Psarakis H.M.
        Clinical challenges in caring for patients with diabetes and cancer.
        Diabetes Spectrum. 2006; 19: 157-162
        • Currie C.J.
        • Poole C.D.
        • Jenkins-Jones S.
        • Gale E.A.
        • Johnson J.A.
        • Morgan C.L.
        Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.
        Diabetes Care. 2012; 35: 299-304
        • Whiting D.R.
        • Guariguata L.
        • Weil C.
        • Shaw J.
        IDF Diabetes Atlas: global estimates of the prevalence of diabetes for 2011 and 2030.
        Diabetes Res Clin Pract. 2011; 94: 311-321