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Gliflozins position update in the treatment algorithms for patients with type 2 diabetes mellitus and chronic kidney disease: new pathogenetic mechanisms and data from subanalyses of the large randomised control trails

https://doi.org/10.14341/DM12864

Abstract

The series of the cardiovascular outcome trails have demonstrated the nephroprotective properties of the gliflozins. Canagliflozin in the CREDENCE, which was the first study with a primary focus on the evaluation of the nephroprotective properties of gliflozin, have demonstrated the possibility to slow the progression of the renal disease. The paper summarizes the additional data from the CREDENCE trail: assessment of the efficacy of canagliflozin by initial eGFR; efficacy in individuals with GFR <30 ml/min/1.73 m2 ; long-term effects of canagliflozin on anaemia-related outcomes; effects of canagliflozin on serum potassium; effects on heart failure and cardiovascular mortality. There are discussed the current treatment algorithms for patients with type 2 diabetes and CKD where using of gliflozins is a priority option. Canagliflozin is a drug with a relatively low ratio of SGLT1/SGLT2 selectivity. The effects of the inhibition of SGLT1 transport in the kidney and in the intestine are described and their additional influence on reducing of the postprandial glycemia and additional nephroprotection.

About the Authors

O. Y. Sukhareva
Endocrinology Research Centre

Olga Y. Sukhareva, MD, PhD

SPIN: 5650-4416

11 Dm. Ulyanova str., Moscow, 117036


Competing Interests:

no



Z. T. Zuraeva
Endocrinology Research Centre
Russian Federation

Zamira T. Zuraeva, MD, PhD

SPIN: 6002-0455

Moscow


Competing Interests:

no



M. S. Shamhalova
Endocrinology Research Centre
Russian Federation

Minara S. Shamhalova, MD, PhD

SPIN: 4942-5481

Moscow


Competing Interests:

no



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Supplementary files

1. Рисунок 1. Натрий-глюкозный котранспортер 1-го типа и NO-синтаза в клетках почечных канальцев в области macula densa [8].
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2. Рисунок 2. Механизм клубочковой гиперфильтрации при внутриканальцевой гипергликемии (ось SGLT1-NOS1-ТГОС в macula densa может опосредовать клубочковую гиперфильтрацию при внутриканальцевой гипергликемии) [8].
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3. Рисунок 3. Эффекты совместного ингибирования натрий-глюкозных котранспортеров 1-го и 2-го типа [9].
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4. Рисунок 4. Динамика показателя расчетной скорости клубочковой фильтрации в исследовании CREDENCE на фоне терапии канаглифлозином 100 мг в подгруппах пациентов с различными исходными показателями (60–<90 мл/мин/1,73 м2, 45–<60 мл/мин/1,73 м2, 30–<45 мл/мин/1,73 м2) [31].
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5. Рисунок 5. Динамика расчетной скорости клубочковой фильтрации у пациентов с исходным значением <30 мл/мин/1,73 м2 в исследовании CREDENCE. Адаптировано G. Bakris, 2020 [32].
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Review

For citations:


Sukhareva O.Y., Zuraeva Z.T., Shamhalova M.S. Gliflozins position update in the treatment algorithms for patients with type 2 diabetes mellitus and chronic kidney disease: new pathogenetic mechanisms and data from subanalyses of the large randomised control trails. Diabetes mellitus. 2021;24(6):553-564. (In Russ.) https://doi.org/10.14341/DM12864

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