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.
Similar content being viewed by others
References
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 29:254–258
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 23:479–484
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 162:259–267
WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech.Rep.Ser. 894:i-253
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 21:1009–1060
Charlson M, Szatrowski T, Peterson T, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47:1245–1251
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 20:44–47
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 348:493–497
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 279:1000–1004
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 92:2462–2470
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305
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 22:477–482
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 5:17–23
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 print
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 352:837–853
Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443
Home PD, Pocock SJ, Beck-Nielsen H et al (2007) Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med 357:28–38
ADVANCE study group (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease—preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120
Conflict of interest statement
Dr. Matteo Monami (MD, PhD) received: (1) speaking fees from Guidotti, Eli Lilly, Merck Sharpe & Dome, Menarini, and Takeda. (2) consultancy fees from Sanofi Aventis and Menarini. Dr. Caterina Lamanna (MD) received: consultancy fees from Merck Sharp & Dome. Dr. Daniela Balzi (MD) has no conflict of interests. Dr. Alberto Marsilii (MD) has no conflict of interests. Prof. Niccolò Marchionni (MD) received: (1) speaking fees from Glaxo Smith and Kline, Guidotti, and Menarini. (2) research grants from Novartis, Novo Nordisk, Sanofi Aventis, Takeda. Dr. Edoardo Mannucci (MD) received: (1) speaking fees from Abiogen Pharma, Glaxo-Smith-Kline, Guidotti, Eli Lilly, Menarini, Merck Sharp & Dome, Merck KgA, Novo Nordisk, Sanofi Aventis, and Takeda. (2) consultancy fees from Sanofi Aventis. (3) research grants from Novartis, Novo Nordisk, Sanofi Aventis, and Takeda. Dr. Mannucci had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Monami, M., Lamanna, C., Balzi, D. et al. Sulphonylureas and cancer: a case–control study. Acta Diabetol 46, 279–284 (2009). https://doi.org/10.1007/s00592-008-0083-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-008-0083-2