Antihyperglycaemic therapies and cancer risk

Abstract

Aims: This review is aimed at highlighting the potential mitogenic/tumour growth-promoting or antimitogenic/tumour growth-inhibiting effects of the main antihyperglycaemic drug classes. Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far. Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers. In contrast, several other drug classes may increase cancer risk. Some reason for concern remains regarding sulphonylureas and also the incretinbased therapies regarding pancreas and thyroid cancers and the sodium glucose cotransporter-2 inhibitors as well as pioglitazone regarding bladder cancer. The majority of meta-analyses suggest that there is no evidence for a causal relationship between insulin glargine and elevated cancer risk, although the studies have been controversially discussed. For α-glucosidase inhibitors and glinides, neutral or only few data upon cancer risk exist. Conclusion: Although the molecular mechanisms are not fully understood, a potential risk of mitogenicity and tumour growth promotion cannot be excluded in case of several antidiabetic drug classes. However, more large-scale, randomized, well-designed clinical studies with especially long follow-up time periods are needed to get reliable answers to these safety issues.

Obesity and Cancer: An Angiogenic and Inflammatory Link

“…Metformin can improve treatment outcomes in preclinical models of cancer, particularly in the obese setting [1,3,58,86,112,118,127,152,164,170,178,181]. In addition, it reduces the incidence of cancer in diabetic patients as well as improves survival in newly diagnosed cases [28,94,97,102,144,152]. Metformin has been shown to target cancer cells, transcription factors, microRNAs, DNA damage, cancer stem cells, and metabolism [29,40,56,77,119,160].…”

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials

“…Furthermore, several glucose-lowering drugs have the potential to affect cancer risk [1]. For example, metformin therapy has been shown to decrease the risk of cancer, while other drugs may increase the risk of specific cancers [4]. Recently, concern was raised about a potential link between thiazolidinediones (e.g.…”

Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment – a clinical appraisal

“…In a summarizing study, Lutz, et al (Lutz, et al, 2014) evaluated cancer risks of the major glucoselowering drug classes and confirmed the trends mentioned above. Favorable effects of metformin on several site-specific cancers were fairly significant, whereas insulin glargine had no effect.…”