Is cancer incidence modified by SGLT2 inhibitors?
Abstract
One of the most important achievements of diabetology in the second decade of the 21st century is undoubtedly the introduction of sodium-glucose cotransporter (SGLT2) inhibitors into clinical practice as a new class of glucose-lowering agents for type 2 diabetes. In addition to the glucosuria induced by these agents, which is their main pathway for achieving ‘antidiabetic recovery’, other consequences accompany the intake of SGLT2 inhibitors. These pathways, particularly in oncology, have not been extensively studied. Considering the analysis of the previous studies, this report demonstrates, although not significantly, that cancer morbidity in patients with T2DM treated with SGLT2 inhibitors may be organ-specific. In addition, agents within the class of SGLT-2 inhibitors may be useful in several variants of antitumor therapy, but this theory requires further study.
About the Author
Lev M. Berstein
N.N.Petrov National Medical Research Center of Oncology
Russian Federation
Russian Federation
MD, PhD, Principap Scientific Researcher of the Laboratory of Oncoendocrinology
References
1. Дедов И.И., Шестакова М.В., Викулова О.К., и др. Распространенность, заболеваемость, смертность, параметры углеводного обмена и структура сахароснижающей терапии по данным Федерального регистра сахарного диабета, статус 2017 г. // Сахарный диабет. — 2018. — Т. 21. — №3. — С. 144-159. [Dedov II, Shestakova MV, Vikulova OK, et al. Diabetes mellitus in Russian Federation: Prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal diabetes register, Status 2017. Diabetes mellitus. 2018;21(3):144-159. (In Russ.)] doi: https://doi.org/10.14341/DM9686
2. Шестакова М.В., Сухарева О.Ю. Глифлозины: особенности сахароснижающего действия и негликемические эффекты нового класса препаратов // Клиническая фармакология и терапия. — 2016. — Т. 25. — №2. — С. 65-71. [Shestakova MV, Sukhareva OY. Gliflozins: glucose-lowering and nonglycemic effects of new class of antidiabetic medications. Klinicheskaia farmakologiia i terapiia. 2016;25(2):65-71. (In Russ.)]
3. Кобалава Ж.Д., Киякбаев Г.К. Сахарный диабет 2 типа и сердечно-сосудистые осложнения: можно ли улучшить прогноз назначением сахароснижающих препаратов // Российский кардиологический журнал. — 2018. — Т. 23. — №8. — С. 79-91. [Kobalava ZD, Kiyakbaev GК. Type 2 diabetes and cardiovascular complications: is it possible to improve prognosis by glucose lovering therapy? Russian Journal of Cardiology. 2018;23(8):79-91. (In Russ.)] doi: 10.15829/1560-4071-2018-8-79-91
4. Kuriyama S. Protection of the kidney with sodium–glucose cotransporter 2 inhibitors: potential mechanisms raised by the large-scaled randomized control trials. Clin Exp Nephrol. 2018;23(3):304-312. doi: https://doi.org/10.1007/s10157-018-1673-0
5. Ishikawa N, Oguri T, Isobe T, et al. SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions. Jpn J Cancer Res. 2001;92(8):874-879. doi: https://doi.org/10.1111/j.1349-7006.2001.tb01175.x
6. Home P. Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia. 2019;62(3):357-369. doi: https://doi.org/10.1007/s00125-018-4801-1
7. Jakher H, Chang TI, Tan M, Mahaffey KW. Canagliflozin review - safety and efficacy profile in patients with T2DM. Diabetes Metab Syndr Obes. 2019;12:209-215. doi: https://doi.org/10.2147/DMSO.S184437
8. Kato ET, Silverman MG, Mosenzon O, et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019;139(22):2528-2536. doi: https://doi.org/10.1161/circulationaha.119.040130
9. Maki T, Maeno S, Maeda Y, et al. Amelioration of diabetic nephropathy by SGLT2 inhibitors independent of its glucose-lowering effect: A possible role of SGLT2 in mesangial cells. Sci Rep. 2019;9(1):4703. doi: https://doi.org/10.1038/s41598-019-41253-7
10. Tang H, Dai Q, Shi W, et al. SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia. 2017;60(10):1862-1872. doi: https://doi.org/10.1007/s00125-017-4370-8
11. Shaikh AMY. SGLT2 inhibitors and cancer: why further evidence is required. Diabetologia. 2017;60(12):2536-2537. doi: https://doi.org/10.1007/s00125-017-4434-9
12. Kohler S, Lee J, George JT, et al. Bladder cancer in the EMPA-REG OUTCOME trial. Diabetologia. 2017;60(12):2534-2535. doi: https://doi.org/10.1007/s00125-017-4430-0
13. Filippas-Ntekouan S, Filippatos TD, Elisaf MS. SGLT2 inhibitors: are they safe? Postgrad Med. 2018;130(1):72-82. doi: https://doi.org/10.1080/00325481.2018.1394152
14. Singh M, Sharma R, Kumar A. Safety of SGLT2 Inhibitors in Patients with Diabetes Mellitus. Curr Drug Saf. 2019;14(2):87-93. doi: https://doi.org/10.2174/1574886314666190206164647
15. De Jonghe S, Proctor J, Vinken P, et al. Carcinogenicity in rats of the SGLT2 inhibitor canagliflozin. Chem Biol Interact. 2014;224:1-12. doi: https://doi.org/10.1016/j.cbi.2014.09.018
16. Shiba K, Tsuchiya K, Komiya C, et al. Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH. Sci Rep. 2018;8(1):2362. doi: https://doi.org/10.1038/s41598-018-19658-7
17. Billger M, Kirk J, Chang J, et al. A study in a rat initiation-promotion bladder tumour model demonstrated no promoter/progressor potential of dapagliflozin. Regul Toxicol Pharmacol. 2019;103:166-173. doi: https://doi.org/10.1016/j.yrtph.2019.01.031
18. Saito T, Okada S, Yamada E, et al. Effect of dapagliflozin on colon cancer cell [Rapid Communication]. Endocr J. 2015;62(12):1133-1137. doi: https://doi.org/10.1507/endocrj.EJ15-0396
19. Kuang H, Liao L, Chen H, et al. Therapeutic Effect of Sodium Glucose Co-Transporter 2 Inhibitor Dapagliflozin on Renal Cell Carcinoma. Med Sci Monit. 2017;23:3737-3745. doi: https://doi.org/10.12659/msm.902530
20. Kaji K, Nishimura N, Seki K, et al. Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake. Int J Cancer. 2018;142(8):1712-1722. doi: https://doi.org/10.1002/ijc.31193
21. Villani LA, Smith BK, Marcinko K, et al. The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration. Mol Metab. 2016;5(10):1048-1056. doi: https://doi.org/10.1016/j.molmet.2016.08.014
22. Scafoglio C, Hirayama BA, Kepe V, et al. Functional expression of sodium-glucose transporters in cancer. Proc Natl Acad Sci U S A. 2015;112(30):E4111-4119. doi: https://doi.org/10.1073/pnas.1511698112
23. Kepe V, Scafoglio C, Liu J, et al. Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas. J Neurooncol. 2018;138(3):557-569. doi: https://doi.org/10.1007/s11060-018-2823-7
24. Scafoglio CR, Villegas B, Abdelhady G, et al. Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma. Sci Transl Med. 2018;10(467). doi: https://doi.org/10.1126/scitranslmed.aat5933
25. Kohler S, Zeller C, Iliev H, Kaspers S. Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials. Adv Ther. 2017;34(7):1707-1726. doi: https://doi.org/10.1007/s12325-017-0573-0
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For citations:
Berstein L.M. Is cancer incidence modified by SGLT2 inhibitors? Diabetes mellitus. 2019;22(4):399-402. (In Russ.)
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