Risk of cancers in the treatment of diabetes mellitus by insulin and sulphonylurea drugs

Authors: Marián Mokáň;  Peter Galajda
Authors‘ workplace: I. interná klinika JLF UK a UNM, Martin
Published in: Forum Diab 2022; 11(3): 151-156
Category: Review Article


Type 2 diabetes mellitus is associated with increased risk of some types of carcinomas mainly carcinoma of liver and pancreas, colorectal carcinoma, breast, endometrial and bladder cancers, which is modulated by antidiabetic treatment. Insulin is important growth factor for cancers, but it is not cancerogenic and it does not cause the development of cancers, however it can promote growth of tumors such growth factor. According to clinical studies insulin and sulphonylurea drugs moderately increase cancer risk compared to metformin, which is decreased by their combination with metformin. Insulin analogues, including insulin glargine not increase cancer risk compared to standard insulin and they are considered as safe from oncologic point of view.


type 2 diabetes mellitus – insulin – risk of cancers – sulphonylurea drugs


1. Draznin B, Aroda VR, Bakris G et al. [American Diabetes Association Professional Practice Committee]. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities – Standards of Medical Care in Diabetes—2022. Diabetes Care 2022; 45(Suppl 1): S46-S59. Dostupné z DOI: <http://dx.doi.org/10.2337/dc22-S004>.

2. Galajda P, Mokáň M. Diabetes mellitus a nádory. Diabetes a obezita 2010; 10(13): 33–43.

3. Galajda P, Mokáň Mi. Michalovičová M et al. Nádorové ochorenia a poruchy metabolizmu glukózy. Quick Print: Martin 2014. 4. Currie CJ, Poole CD, Gale AM. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009; 52(9): 1766–1777. <Dostupné z DOI: http://dx.doi.org/10.1007/s00125–009–1440–6Z>.

5. Donadon V, Balbi M, Ghersetti M et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol 2009; 15(20): 2506–2511. Dostupné z DOI: <http://dx.doi.org/10.3748/wjg.15.2506>.

6. Kawaguchi T, Taniguchi E, Morita Y et al. Association of exogenous insulin or sulphonylurea treatment with an increased incidence of hepatoma in patients with hepatitis C virus infection. Liver International 2009; 30(3): 479–486. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1478–3231.2009.02191.x>.

7. Hassan MM, Curley SA, Li D et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 2010; 116(8): 1938–1946. Dostupné z DOI: <http://dx.doi.org/10.1002/cncr.24982>.

8. Yang XX, Henessy S, Lewis JD. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology 2004; 127(4): 1044–1050. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2004.07.011>.

9. Schiel R, Mullar UA, Braun A et al. Risk of malignancies in patients with insulin-treated diabetes mellitus. Eur J Med Res 2005; 10(8): 339–344.

10. Chung YW, Han DS, Park KH et al. Insulin therapy and colorectal adenoma risk among patients with type 2 diabetes mellitus: a case-control study in Korea. Dis Colon Rectum 2008; 51(5): 593–597. Dostupné z DOI: <http://dx.doi.org/10.1007/s10350–007–9184–1>.

11. Vinikoor LC, Long MD, Keku TO et al. The association between diabetes, insulin use and colorectal cancer among whites and African American. Cancer Epidemiol Biomarkers Prev 2009; 18(4): 1239–1242. Dostupné z DOI: <http://dx.doi.org/10.1158/1055–9965.EPI-08–1031>.

12. Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer 2007; 96(3): 507–509. Dostupné z DOI: <http://dx.doi.org/10.1038/sj.bjc.6603571>.

13. Zendehdel K, Nyren O, Ostenson CG et al. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 2003; 95(23): 1797–1800. Dostupné z DOI: <http://dx.doi.org/10.1093/jnci/djg105>.

14. Janssen JA, Varewijck AJ. Insulin analogs and cancer: a note of caution. Front Endocrinol (Lausanne) 2014; 5: 79. Dostupné z DOI: <http://dx.doi.org/10.3389/fendo.2014.00079>.

15. Sciacca L, Vella V, Frittitta L et al. Long-acting insulin analogs and cancer. Nutr Metab Cardiovasc Dis 2018; 28(5): 436–443. Dostupné z DOI: <http://dx.doi.org/10.1016/j.numecd.2018.02.010>.

16. Agin A, Jeandidier N, Gasser F et al. Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay. Diabetes Metabol 2007; 33(3): 205–212. Dostupné z DOI: <http://dx.doi.org/10.1016/j.diabet.2006>.

17. Sommerfeld MR, Mullar G, Tschank G et al. In vitro metabolic and mitogenic signalling of insulin glargine and its metabolites. PLoS One 2010; 5(3): e9540. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0009540>.

18. Hemkens LG, Grouven U, Bender R et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetelogia 2009; 52(9): 1732–1744. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–009–1418–4>.

19. Coulhoun HM. [SDRN Epidemiology Group]. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia 2009; 52(9): 1755–1765. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–009–1453–1>.

20. Rosenstock J, Fonseca V, McGill JB et al. Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: Finding from a 5 year randomised open-label study. Diabetologia 2009; 52(9): 1971–1973. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–009–1452–2>.

21. Home PD, Lagarenne P. Combined randomised controlled trial experience of malignancies in studies using insulin glargine. Diabetologia 2009; 52(12): 2499–2506. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–009–1530–5>.

22. Jonansson JM, Ljung R, Talback M et al. Insulin glargine use and short-term incidence of malignancies – a population-based follow up study in Sweden. Diabetologia 2009; 52(9): 1745–1754. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–009–1444–2>.

23. Ljung R, Talbäck M, Haglund B et al. Insulin glargine use and shortterm incidence of malignancies – a three-year population-based observation. Acta Oncol 2011; 50(5): 685–693. Dostupné z DOI: <http://dx.doi.org/10.3109/0284186X.2011.558913>.

24. Ljung R, Talbäck M, Haglund B et al. Insulin glargine use and shortterm incidence of breast cancer – a four-year population-based observation. Acta Oncol 2012; 51(3): 400–402. Dostupné z DOI: <http://dx.doi.org/10.3109/0284186X.2011.624118>.

25. Suissa S, Azoulay L, Dellaniello S et al. Long-term effects of insulin glargine on the risk of breast cancer. Diabetologia 2011; 54(9): 2254–2262. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–011–2190–9>.

26. Ruiter R, Visser LE, van Herk-Sukel MP 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(1): 51–62. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–011–2312–4>.

27. Fahot JP, Blotiera PO, Ricordeau P et al. Does insulin glargine increase the risk of cancer compared with other basal insulins? A French nationwide cohort study based on national administrative databases. Diabetes Care 2013; 36(2): 294–301. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0506>.

28. Du X, Zhang R, Xue Y et al. Insulin glargine and risk of cancer: a meta-analysis. Int J Biol Markers 2012; 27(3): e241-e246. Dostupné z DOI: <http://dx.doi.org/10.5301/JBM.2012.9349>.

29. Gerstein HC, Bosch J, Dagenais GR et al. [ORIGIN Trial Investigators]. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 201; 367(4): 319–328. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1203858>.

30. But A, De Bruin ML, Bazelier MT et al. Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study. Diabetologia 2017; 60(9): 1691–1703. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–017–4312–5>.

31. Dejgaard A, Lyngaard H, Rastam J et al. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009; 52(12): 2507–2512. Dostupné z DOI: <http://dx.,doi.org/10.1007/s00125–009–1568–4>.

32. Monami M, Mannucci E. Efficacy and safety of degludec insulin: a meta-analysis of randomised trials. Curr Med Res Opin 2013; 29(4): 339–342. Dostupné z DOI: <http://dx.doi.org/10.1185/03007995.2013.772507>.

33. Qian X, Li J, Ding J et al. Glibenclamide exerts an antitumor activity through oxygen species c-jun NH(2)-terminal kinase pathway in human gastric cancer cell line MGC-803. Biochem Pharmacol 2008; 76(12): 1705–1715. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bcp.2008.09.009>.

34. Bowker SL, Majumdar SR, Veugelers P et al. Increased cancer – related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006; 29(2): 254–258. Dostupné z DOI: <http://dx.doi.org/10.2337/diacare.29.02.06.dc05–1558>.

35. Tuccori M, Wu JW, Yin H et al. The use of glyburide compared with other sulfonylureas and the risk of cancer in patients with type 2 diabetes. Diabetes Care 2015; 38(11): 2083–2089. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1358>.

36. Monami M, Balzi D, Lamanna C et al. Are sulphonylureas all the same? A cohort study on cardiovascular and cancer-related mortality. Diabetes Metab Res Rev 2007; 23: 479–484. Dostupné z DOI: <http://dx.doi.org/10.1002/dmrr.736>.

37. Monami M, Lamanna C, Balzi D et al. Sulphonylureas and cancer: a case-control study. Acta Diabetol 2009; 46(4): 279–284. Dostupné z DOI: <http://dx.doi.,org/10.1007/s00592–008–0083–2>.

38. Yang X, So WY, Ma RC et al. Use of sulphonyurea and cancer in type 2 diabetes – The Hong Kong Diabetes Registry. Diabetes Res Clin Pract 2010; 90(3): 343–351. Dostupné z DOI: <http://dx.doi.org/10.1016/j.diabres.2010.08.022>.

39. Bo S, Catiglkione A, Chigo E et al. Mortality outcomes of different sulfonylurea drugs? The results of a 14-year cohort study of type 2 diabetic patients. Eur J Endocrinol 2013; 169(1): 117–126. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-13–0299>.

40. Du J, Kleefstra N, Schrijnders D et al. Is gliclazide associated with a lower obesity-related cancer risk compared to other sulfonylureas? A long-term prospective cohort study. Cancer Epidemiol Biomarkers Prev 2020; 29(8): 1596–1605. Dostupné z DOI: <http://dx.doi.org/10.1158/1055–9965.EPI-19–1517>.

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