Study of the Association Between Antihyperglycemic Therapy and Cancer in Patients with Type 2 Diabetes Mellitus


antihyperglycemic therapy

How to Cite

Vatseba, T., Sokolova, L., Pushkarev, V., & Koshel, N. (2020). Study of the Association Between Antihyperglycemic Therapy and Cancer in Patients with Type 2 Diabetes Mellitus. Galician Medical Journal, 27(3), E202033.


The objective of the research was to investigate the features and association of antihyperglycemic therapy and cancer in patients with type 2 diabetes mellitus.

Materials and Methods. The study included the analysis of medical records of patients with type 2 diabetes mellitus who were diagnosed with cancer during 2012-2016. The obtained results were processed by statistical methods using the software packages Microsoft Excel and Statistika-12. The significance of differences between the frequency of using different treatment schemes was assessed by the Pearson’s test (χ²). To determine the risk of predicted events, the odds ratio, the 95% confidence interval, the positive and negative prognostic values were calculated.

Results. There were diagnosed 533 cases of cancer in patients with type 2 diabetes mellitus. The most common scheme of antihyperglycemic therapy prior to the detection of malignant diseases was a combination of metformin and sulfonylurea derivatives (35.65%), as well as monotherapy with sulfonylurea derivatives (17.26%) and metformin (11.28%). Prior to diagnosing cancer in 396 (74.30%) patients, antihyperglycemic therapy
along with sulfonylurea derivatives and insulin was used. Among obese patients 68.82% used sulfonylureas and insulin as part of antidiabetic therapy before diagnosis of cancer. The connection between insulin therapy and the risk of cancer development in patients with type 2 diabetes mellitus was proved (the odds ratio=2.35; the 95% confidence interval (1.91 - 2.91); p<0.001).

Conclusions. Prior to the detection of cancer in patients with type 2 diabetes mellitus, the combination therapy with metformin and sulfonylurea derivatives was most often used. The association between insulin therapy and the development of cancer in patients with type 2 diabetes mellitus was revealed. Cancer screening is advisable for patients with type 2 diabetes mellitus and obesity, who receive as a therapy sulfonylurea derivates and/or insulin.


Pushkarev VM, Sokolova LK, Pushkarev VV et al. Biochemical mechanisms connecting diabetes and cancer. Effects of methormine. Endocrinology. 2018; 23 (2): 167-179. [published in Russian]

Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017; 169 (3): 381-405. DOI: [PMid:28431241 PMCid:PMC5546324]

Vatseba TS. The role of insulin, IGF-1 and PRAS40 in the processes of oncogenesis in women with diabetes mellitus type 2 and endometrial cancer. Galician Medical Journal. 2019; 26 (4): 7-11. DOI:

Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011; 12 (1): 21-35. DOI: [PMid:21157483 PMCid:PMC3390257]

Yao L, Liu M, Huang Y et al. Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis. Dis Markers. 2019; 6230162. DOI: [PMid:30881522 PMCid:PMC6387718]

Liu F, Yan L, Wang Z et al. Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis. Oncotarget. 2017; 8 (9): 16017-16026. DOI: [PMid:27926481 PMCid:PMC5362542]

Tseng CH. Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2015; 31 (6): 619-626. DOI: [PMid:25820555]

Tseng CH. Metformin may reduce breast cancer risk in Taiwanese women with type 2 diabetes. Breast Cancer Res Treat. 2014; 145 (3): 785-790. DOI: [PMid:24816805]

Tian J, Liang Y, Qu P. Antidiabetic Medications and the Risk of Endometrial Cancer in Patients. Gynecol Obstet Invest 2019; 84: 455-462. DOI: [PMid:30808843]

Vatseba TS. Cancer of the organs of the reproductive system in women with type 2 diabetes. Effects of antidiabetic therapy. Wiadomości Lekarskie. 2020;73(5): 967-971.

Mekuria AN, Ayele Y, Tola A et al. Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis. J Diabetes Res. 2019; 7676909. DOI: [PMid:31828167 PMCid:PMC6885827]

Dąbrowski M, Szymańska-Garbacz E, Miszczyszyn Z et al. Antidiabetic medications use and cancer risk in type 2 diabetes. Clinical Diabetology. 2017; 6 (1): 17-25. DOI:

Colmers IN, Bowker SL, Tjosvold LA et al. Insulin use and cancer risk in patients with type 2 diabetes: a systematic review and meta-analysis of observational studies. Diabetes Metab. 2012; 38 (6): 485-506. DOI: [PMid:23159131]

Hendriks AM, Schrijnders D, Kleefstra N et al. Sulfonylurea derivatives and cancer, friend or foe?. Eur J Pharmacol. 2019; 861: 172598. DOI: [PMid:31408647]

Song CW, Lee H, Dings RP et al. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Sci Rep. 2012; 2: 362. DOI: [PMid:22500211 PMCid:PMC3324825]

Thakkar B, Aronis KN, Vamvini MT et al. Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies. Metabolism. 2013; 62 (7): 922-934. DOI: [PMid:23419783]

Pasello G, Urso L, Conte P et al. Effects of sulfonylureas on tumor growth: a review of the literature. Oncologist. 2013; 18 (10): 1118-1125. DOI: [PMid:24043597 PMCid:PMC3805154]

Call R, Grimsley M, Cadwallader L et al. Insulin--carcinogen or mitogen? Preclinical and clinical evidence from prostate, breast, pancreatic, and colorectal cancer research. Postgrad Med. 2010; 122 (3): 158-165. DOI: [PMid:20463425]

Singh S, Singh H, Singh PP et al. Antidiabetic medications and the risk of colorectal cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2013; 22 (12): 2258-2268. DOI: [PMid:24042261]

Tseng CH. Prolonged use of human insulin increases breast cancer risk in Taiwanese women with type 2 diabetes. BMC Cancer. 2015; 15: 846. DOI: [PMid:26537234 PMCid:PMC4632264]

Kurtzhals P, Schä ffer L, Sø rensen A et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 2000; 49 (6): 999-1005. DOI: [PMid:10866053]

Grimaldi-Bensouda L, Cameron D, Marty M et al. ISICA Group. Risk of breast cancer by individual insulin use: an international multicenter study. Diabetes Care. 2014; 37 (1): 134-143. DOI: [PMid:23949559]

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. DOI: [PMid:28573394 PMCid:PMC5552833]

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