Acta Diabetologica

, 46:279

Sulphonylureas and cancer: a case–control study

  • Matteo Monami
  • Caterina Lamanna
  • Daniela Balzi
  • Niccolò Marchionni
  • Edoardo Mannucci
Original Article

Abstract

This study was aimed at the assessment of incidence of malignancies in type 2 diabetic patients treated with different sulphonylureas. A matched case–control study was performed. Cases were 195 diabetic patients aged 69.0 ± 9.2 years who had an incident malignancy. Controls were 195 diabetic patients, unaffected by cancer, who were matched with the corresponding case for age, sex, duration of diabetes, BMI, HbA1c, comorbidity, smoking and alcohol abuse. Exposure to hypoglycaemic drugs during the 10 years preceding the event (or matching index date) was assessed. After adjusting for concomitant therapies, exposure to metformin and gliclazide for more than 36 months was associated with a significant reduction in the risk of cancer (adj. ORs with 95% CI: 0.28 (0.13–0.57), p < 0.001, and 0.40 (0.21–0.57), p = 0.004, respectively). Conversely, use of glibenclamide for at least 36 months was associated with increased incidence of malignancies (adj. OR 2.62 (1.26–5.42); p = 0.009). Treatment with insulin, thiazolidinediones, or acarbose, was not associated with significant differences in the incidence of cancer. Long-term treatments with individual sulphonylureas could have differential effects on the risk of cancer. In particular, the possible protective effect of gliclazide, as well as the risk associated with glibenclamide, deserves further investigation.

Keywords

Cancer Diabetes mellitus Case–control study Hypoglycaemic Drugs Sulphonylureas 

References

  1. 1.
    Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29:254–258CrossRefPubMedGoogle Scholar
  2. 2.
    Monami M, Balzi D, Lamanna C et al (2007) Are sulphonylureas all the same? A cohort study on cardiovascular and cancer-related mortality. Diabetes Metab Res Rev 23:479–484CrossRefPubMedGoogle Scholar
  3. 3.
    Sliwinska A, Blasiak J, Drzewoski J (2006) Effect of gliclazide on DNA damage in human peripheral blood lymphocytes and insulinoma mouse cells. Chem Biol Interact 162:259–267CrossRefPubMedGoogle Scholar
  4. 4.
    WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech.Rep.Ser. 894:i-253Google Scholar
  5. 5.
    Chalmers J, MacMahon S, Mancia G et al (1999) World Health Organization-International Society of Hypertension Guidelines for the management of hypertension: guidelines sub-committee of the World Health Organization. Clin Exp Hypertens 21:1009–1060CrossRefPubMedGoogle Scholar
  6. 6.
    Charlson M, Szatrowski T, Peterson T, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47:1245–1251CrossRefPubMedGoogle Scholar
  7. 7.
    Mannucci E, Monami M, Masotti G, Marchionni N (2004) All-cause mortality in diabetic patients treated with combinations of sulfonylureas and biguanides. Diabetes Metab Res Rev 20:44–47CrossRefPubMedGoogle Scholar
  8. 8.
    Pahor M, Guralnik JM, Ferrucci L, Corti MC, Salive ME, Cerhan JR et al (1996) Calcium-channel blockade and incidence of cancer in aged populations. Lancet 348:493–497CrossRefPubMedGoogle Scholar
  9. 9.
    Rosenberg L, Rao RS, Palmer JR, Strom BL, Stolley PD, Zauber AG, Warshauer ME, Shapiro S (1998) Calcium channel blockers and the risk of cancer. JAMA 279:1000–1004CrossRefPubMedGoogle Scholar
  10. 10.
    Friis S, Sørensen HT, Mellemkjaer L, McLaughlin JK, Nielsen GL, Blot WJ, Olsen JH (2001) Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark. Cancer 92:2462–2470CrossRefPubMedGoogle Scholar
  11. 11.
    Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305CrossRefPubMedGoogle Scholar
  12. 12.
    Monami M, Luzzi C, Lamanna C et al (2006) Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin. Diabetes Metab Res Rev 22:477–482CrossRefPubMedGoogle Scholar
  13. 13.
    Ramos-Nino ME, Maclean CD, Littenberg B (2007) Association between cancer prevalence and use of thiazolidinediones (TZDs): results from the vermont diabetes information system. BMC Med 5:17–23CrossRefPubMedGoogle Scholar
  14. 14.
    Monami M, Lamanna C, Marchionni N, Mannucci E (2008) Rosiglitazone and risk of cancer: a meta-analysis of randomized clinical trials. Diabetes Care Epub ahead of printGoogle Scholar
  15. 15.
    UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRefGoogle Scholar
  16. 16.
    Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443CrossRefPubMedGoogle Scholar
  17. 17.
    Home PD, Pocock SJ, Beck-Nielsen H et al (2007) Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med 357:28–38CrossRefPubMedGoogle Scholar
  18. 18.
    ADVANCE study group (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease—preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120Google Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Matteo Monami
    • 1
  • Caterina Lamanna
    • 1
  • Daniela Balzi
    • 2
  • Niccolò Marchionni
    • 1
  • Edoardo Mannucci
    • 1
  1. 1.Department of Critical Care Medicine and Surgery, Unit of Gerontology and GeriatricsUniversity of Florence and Azienda Ospedaliero-Universitaria CareggiFlorenceItaly
  2. 2.Epidemiology UnitFlorenceItaly

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