Sulfonylurea derivatives and cancer, friend or foe?

Hendriks, Anne M.; Schrijnders, Dennis; Kleefstra, Nanne; Vries, Elisabeth G.E. de; Bilo, Henk J. G.; Jalving, Mathilde; Landman, Gijs W. D.

doi:10.1016/j.ejphar.2019.172598

Cited by 35 publications

(27 citation statements)

References 118 publications

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“…However, according to a comparative metaanalysis of many studies, the risk of cancer in patients taking SUD is ambiguous and depends on the generation of drugs, their affinity with receptors of the pancreas and differentiated insulin exposition [14].…”

Section: Resultsmentioning

confidence: 99%

“…In addition, SUD reduce the level of TNFα and the number of TNFα receptors in cancer cells, having a beneficial effect on the tumor microenvironment. It has been also proven that drugs of this group have antioxidant effect, which is due to their effect on ATP-dependent K+channels and activation of antioxidant systems of the body that can inhibit cell growth by inducing apoptosis [14,17]. These effects can be very useful in the treatment of cancer, but only for those who have no hyperinsulinemia.…”

Section: Resultsmentioning

confidence: 99%

“…Studies proved the prooncogenic effect of drugs in this group due to the effects of hyperinsulinemia [11,12]. The role of iatrogenic hyperinsulinemia (as a result of insulin therapy) as a factor of oncogenesis has been proven in many studies [13], but the results of some studies differ [14].…”

Section: Problem Statement and Analysis Of The Latest Researchmentioning

confidence: 99%

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

et al. 2020

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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 therapyalong 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…Sulfonylureas might also be associated with a greater risk of cancer compared to DPP-4 inhibitors and TZDs [19]. On the other hand, according to a recent review, some sulfonylureas have a protective effect against cancer by reducing the growth of cancer cells, inhibiting tumour necrosis factor (TNF) production by human peripheral blood mononuclear cells and by inhibition of TNF bioactivity and immunoreactivity in mice serum [20].…”

Section: Introductionmentioning

confidence: 99%

A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk

Dulskas

Patašius

Kaceniene

et al. 2020

JCM

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We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.

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“…A lot of studies have shown an increased risk of cancer in patients who undergo sulfonylurea (SU) therapy due to its ability to stimulate insulin release, leading to hyperinsulinemia [5]. However, some studies prove the potential oncoprotective properties of SU derivatives related to their mechanism of action, in particular through their ability to suppress VEGF and neovascularization of malignant neoplasms (MN), reduce tumor necrosis factor-α (TNF-α) levels and the amount of receptors for TNF-α in cancer cells (affecting tumor microenvironment), and due to their antioxidant effects [6].…”

Section: Introductionmentioning

confidence: 99%