Single article

Shumilova N., Pavlova S.

Glyphosine derivatives: glycemic and non-clycemic effects

Keywords: type 2 diabetes, SGLT2, glyphozine derivatives, SGLT2 inhibitors, Dapagliflozinum, Empagliflozinum, Canagliflozinum

In the world there is a tendency of increase in the incidence of type 2 diabetes. The search for new hypoglycemic agents with maximum efficiency and minimal side effects continues. There appeared a new class of hypoglycemic agents – inhibitors of sodium/glucose cotransporter of type 2 in the kidneys (SGLT2), which reduce plasma glucose levels by reducing its reabsorption in the proximal renal tubules. Decrease of glucose in blood occurs independently of insulin and pancreatic beta-cells’ functioning. In Russia Dapagliflozinum, Empagliflozinum, Canagliflozinum are registered. Clinical trials of these drugs have shown their effectiveness in reducing glycemia and glycated hemoglobin in type 2 diabetic patients. In addition, glyphosine derivatives showed a number of positive non-glycemic effects: decrease in body weight, in the risk of cardiovascular complications in type 2 diabetic patients. Glyphosine derivatives are characterized by a low risk of adverse effects. Glyphosine derivatives are well tolerated by patients and rarely cause hypoglycemic states in patients with type 2 diabetes. The most frequent complications were urinary tract infections, and the rarest was ketoacidosis.

References

  1. Amosova M.V., Fadeev V.V. Empagliflozin – novye pokazaniya k primeneniyu – povorot-nyi moment v lechenii sakharnogo diabeta 2-go tipa [A new indication for empagliflozin: turning point in the treatment of type 2 diabetes]. Medicinskiy sovet, 2017, no. 3, pp. 38–43.
  2. Bukatina T.M., Kazakov A.S., Vel’ts N.Yu., Darmastukova M.A., Kolesnikova E.Yu., Alyautdin R.N., Romanov B.K. Ingibitory natrii-glyukoznogo kotransportera 2: risk keto-atsidoza [Inhibitors of sodium-glucose cotransporter 2: risk of ketoacidosis]. Bezopasnost’ i risk farmakoterapii [Safety and Risk of Phamacotherapy], 2016, no. 2, pp. 33–39.
  3. Druk I.V., Nechaeva G.I. Snizhenie serdechno-sosudistyh riskov pri saharnom diabete 2 tipa: novyj klass saharosnizhayushchih preparatov – novye perspektivy [Reduction of cardiovascular risks in 2nd type diabetes mellitus: new class of antihyperglycemic drugs – new prospects]. Lechashshchij vrach, 2015, no. 12, pp. 39–44.
  4. Mkrtumyan A.M., Yegshatyan L.V. Novyj neinsulinzavisimyi podhod k terapiisaharnogo diabeta 2 tipa. Dapagliflozin: rezul’taty klinicheskih issledovanij [A Novel non-insulin dependent approach to therapy of type 2 diabetes mellitus. Dapagliflozin: results of clinical trials]. Effeektivnaya farmakoterapiya [Effective Pharmacotherapy], 2015, no. 11, pp. 17–25.
  5. Halimov Yu.Sh., Agafonov P.V., Kuzmich V.G. Rol’ I mesto dapagliflozina v upravlenii saharnym diabetom 2-go tipa: ot teorii k praktike [Role and place of dapagliflozin in the menegement of 2nd type diabetes: from theory to practice]. Medicinskiy sovet, 2017, no. 3, pp. 22–30.
  6. Sharonova L.A., Verbovoy A.F., Verbovaya N.I. et al. Ingibitory natrij-glyukoznyh kotransporterov-2 – novye vozmozhnosti v lechenii pacienta s saharnym diabetom 2 tipa [Sodium-glucose cotransporter inhibitors 2 – new opportunities in the treatment of patients with type 2 diabetes]. Vestnik medicinskogo instituta “REAVIZ”, 2017, no. 5, pp. 129–134.
  7. Shestakova M.V., Sukhareva O.Yu. Gliflozini: osobennosti saharosnizhayushchego dejstviya I neglikemicheskie ehffekty novogo klassa preparatov [Gliflozins: glucose-loweverin and nonglycemic effects of new class of antidiabetic medications]. Klinicheskaya farmakologiya I terapiya, 2016, vol. 25, no. 2, pp. 65–71.
  8. Alsahli M., Gerich J.E. Renal glucose metabolism in normal physiological conditions and in diabetes. Diabetes Research and Clinical Practice, 2017, vol. 133, pp. 1–9.
  9. Ferrannini E. Sodium Glucose co-transporters and their inhibition: clinical physiology. Cell Metabolism., 2017, vol. 26, no. 5, pp. 27–37.
  10. Goldenberg R.M. Berard L.D., Cheng A.Y.Y., Gilbert J.D., Verma S., Woo V.C. et al. SGLT2 inhibitor – associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clinical Therapeutics, 2016, vol. 38, no. 12, 2654–2664.
  11. Y., Babu A.R. Clinical potential of sodium-glucose cotransporter 2 inhibitor canagliflosin in the management of type 2 diabetes. Diabetes Metab Syndr Obes., 2012, no. 5, pp. 313–327.
  12. Lopaschuk G.D., Verma S. Empagliflozin’s fuel hypothesis: not so soon. Cell Metabolism., 2016, vol. 24. pp. 200–202.
  13. Ohgaki R., Wei L., Yamada K., Hara T., Kuriyama C., Okuda S. et al. Interaction of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflosin with SGLT1 and SGLT2: inhibition kinetics, sidedness of action and transporter-associated incorporation accounting for its pharmacodynamics and pharmacokinetic features. Pharmacol. Exp. Ther., 2016, vol. 358, pp. 94–102.
  14. Perrone-Filardi P., Avogaro A., Bonora E., Colivicchi F., Fioretto P., Maggioni A.P. et al. Mechanisms linking empagliflozin to cardiovascular and renal protection. International Journal of Cardiology, 2017, vol. 241, pp. 450–456.
  15. Rieg T., Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia, 2018, vol. 61, pp. 2079–2086.
  16. Staels B. Cardiovascular protection by sodium glucose cotransporter 2 inhibitors: potential mechanisms. J. Cardiol., 2017, vol. 120, pp. 28–36.
  17. Thynne T., Doogue M. Sodium-glucose co-transporter inhibitors; mechanisms of action. Prescr., 2013, vol. 37, pp. 14–20.
  18. Wilding J.P.H. The role of the kidneys in glucose homeostasis in type 2 diabetes: clinical implications and therapeutic significance though sodium glucose co-transporter 2 inhibitors. Metabolism clinical and experimental., 2014, vol. 63, 10, pp. 1214–1237.
  19. Wataru Ogawa, Kazuhiko Sakaguchi. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. Diabetes Investig., 2016, vol. 7, no.2, pp. 135–138.
  20. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. Available at: https://www.fda.gov/DrugSafety/ucm617360.

About authors

Shumilova Nadezhda A.
Senior Lecturer, Pharmacology, Clinical Pharmacology and Biochemistry Department, Chuvash State University, Russia, Cheboksary (pharmamail@yandex.ru; )
Pavlova Svetlana I.
Doctor of Medical Sciences, Head of the Department of Pharmacology, Clinical Pharmacology and Biochemistry, Chuvash State University, Russia, Cheboksary (flavonoid@yandex.ru; ORCID: https://orcid.org/0000-0001-9976-7866)

Article link

Shumilova N., Pavlova S. Glyphosine derivatives: glycemic and non-clycemic effects [Electronic resource] // Acta medica Eurasica. – 2019. – №1. P. 44-51. – URL: https://acta-medica-eurasica.ru/en/single/2019/1/6/.