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Antidiabetic drugs and risk of cancer

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Abstract

Antidiabetic drugs are an important group of medications used worldwide. They differ from each other in the mechanisms of lowering blood glucose as well as in adverse effects that may affect the course of the treatment and its efficacy. In recent years, new drugs have been discovered in order to improve the maintenance of proper blood glucose level and to reduce unwanted effects of these drugs. Their growing administration is related to the increasing incidence of diabetes observed in all countries in the world. Epidemiological data indicate that diabetes increases the risk of cancer, as well as the risk of death linked with neoplasms. It is still unknown whether this is an effect of antidiabetic drugs or just the effect of diabetes itself. In recent years there have been numerous investigations and meta-analyzes, based on both comparative and cohort studies trying to establish the relationship between antidiabetic pharmacotherapy and the incidence and mortality due to cancer. According to their findings, most of antidiabetic drugs increase the risk of cancer while only few of them show antitumor properties. Different mechanisms of action of glucose-lowering drugs may be responsible for these effects. However, most of the published studies concerning the influence of these drugs on cancer incidence were designed with some limitations and differed from each other in the approach.

In this review, we discuss the association between antidiabetic drugs used in monotherapy or polytherapy and cancer risk, and consider potential mechanisms responsible for the observed effects.

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Abbreviations

ATP:

adenosine triphosphate

BMI:

body mass index

CI:

confidence interval

DDDs:

defined daily doses

DNA:

deoxyribonucleic acid

DPP-4 inhibitors:

dipeptidyl peptidase-4 inhibitors

Egr-1:

early growth response-1 transcription factor

FDA:

Food and Drug Administration

GLP-1 agonists:

glucagon-like peptide-1 agonists

HR:

hazard ratio

IGF-1R:

insulin-like growth factor 1 receptor

IR:

insulin receptor

IU:

international unit

mTOR:

mammalian target of rapamycin

OR:

odds ratio

PPAR γ:

peroxisome proliferator-activated receptor gamma

p :

p-value (probability value)

RR:

relative risk

SC:

subcutaneous injection

SGLT2 inhibitors:

sodium/glucose cotransporter 2 inhibitors

SIR:

standardized incidence ratio

T2DM:

type 2 diabetes mellitus

TZDs:

thiazolidinediones

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Authors and Affiliations

  1. Department of Experimental Pharmacology, Medical University of Białystok, Białystok, Poland

    Anna Tokajuk, Edyta Krzyżanowska-Grycel, Adrian Tokajuk, Anna Sadowska & Halina Car

  2. Department of Diabetology, Endocrinology and Internal Medicine, J. Sniadecki Hospital, Białystok, Poland

    Sławomir Grycel

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Tokajuk, A., Krzyżanowska-Grycel, E., Tokajuk, A. et al. Antidiabetic drugs and risk of cancer. Pharmacol. Rep 67, 1240–1250 (2015). https://doi.org/10.1016/j.pharep.2015.05.005

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