Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Shestakova, Marina Vladimirovna; Аметов, А.С.; Antsiferov, M. B.; Bardymova, T. P.; Валеева, Ф. В.; Galstyan, Gagik R.; Demidova, T. Yu.; Карпова, И. А.; Kiseleva, T. P.; Mayorov, Alexander Yur'evich; Mkrtumyan, А. M.; Nedogoda, S. V.; Petunina, N. A.; Ruyatkina, Lyudmila A.; Суплотова, Л. А.; Sukhareva, Olga Yur'evna; Фадеев, В. В.; Шамхалова, Минара Шамхаловна

doi:10.14341/dm12848

Cited by 2 publications

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“…Кардиопротективные эффекты связывают с их действием на сердечный натрий-протонный обменник NHE1 [ 46 ]. Важно отметить, что кардиопротективный эффект НГЛТ-2 наблюдается и у больных без СД [ 3 ][ 46 ].…”

Section: общая характеристика ингибиторов нглт-2unclassified

“…В настоящее время НГЛТ-2 представляют фармакотерапевтическую группу, важную для лечения диабета и профилактики его осложнений [ 3 ][ 46 ][ 47 ], а препараты, одновременно ингибирующие НГЛТ-2 и НГЛТ-1, такие как канаглифлозин и сотаглифлозин, остаются еще более интересными для клинического применения [ 3 ].…”

Section: общая характеристика ингибиторов нглт-2unclassified

“…Препараты этой группы имеют высокий терапевтический потенциал, инсулиннезависимый механизм действия, эффективно снижают уровень глюкозы в крови и гликированного гемоглобина, массу тела, артериальное давление (АД), уровень мочевой кислоты [ 3 ]. Ингибиторов НГЛТ-2 от других гипогликемических препаратов отличает широкий спектр плейотропных свойств.…”

Section: класс-специфические свойства препаратов ингибирующих нглт-2unclassified

“…Ингибиторы НГЛТ-2 являются жирорастворимыми веществами и хорошо проникают в мозг, где взаимодействуют с НГЛТ и поэтому уменьшают неврологические осложнения [ 48 ][ 51 ]. Это определило их место в терапии СД 2 типа, с указанными сопутствующими патологиями [ 3 ][ 44 ]. Важными свойствами ингибиторов НГЛТ-2 является их способность улучшать липидный обмен [ 4 ], снижать инсулинорезистентность [ 52 ], массу тела [ 47 ][ 53 ].…”

Section: класс-специфические свойства препаратов ингибирующих нглт-2unclassified

“…Однако более чем у 2/3 пациентов не удается достичь целевых значений гликемии, также не всегда удается предупредить потерю β-клеток поджелудочной железы и многочисленные осложнения СД. Это побуждает искать новые мишени и новые препараты, использовать комбинированную терапию, разрабатывать новые стратегии и новые технологии лечения СД [ 1 ][ 3 ][ 4 ].…”

Section: Introductionunclassified

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Synergistic effects of GABA and hypoglycemic drugs

Tyurenkov,

Faibisovich,

Bakulin

2023

Probl Endokrinol (Mosk)

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Diabetes mellitus (DM) is the leading cause of premature death and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing the level of glycemia and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of DM and its complications continues. Significant resources are used to develop new drugs, but recently the possibility of using «old» widely available drugs with newly discovered pleiotropic properties has been substantiated. These may include preparations of gammaaminobutyric acid (GABA) and agents that directly or indirectly activate GABAergic transmission, which have a pronounced pancreatic protective effect, which has been widely discussed in foreign literature over the past 10–15 years. However, there are few such publications in the domestic literature.It has been established that the content of GABA in β-cells in patients with type 1 and type 2 diabetes is reduced and this correlates with the severity of the disease. Genetic suppression of GABA receptors causes a significant decrease in the mass of β-cells and glucose-stimulated insulin secretion, which confirms the importance of GABA in ensuring glucose homeostasis and the advisability of replenishing the GABA deficiency in DM with its additional administration. It has been established that in animals with DM, GABA suppresses apoptosis and stimulates the regeneration of β-cells, increases β-cell mass and insulin production.Experimental data have been obtained indicating a synergistic effect of GABA when combined with glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, when a more pronounced pancreoprotective effect is observed, due to decrease in oxidative and nitrosative stress, inflammation, increase in the level of Klotho protein, Nrf-2 activity and antioxidant defense enzymes, suppression of NF-kB activity and expression of pro-inflammatory cytokines. As a result, all this leads to a decrease in apoptosis and death of β-cells, an increase in β-cell mass, insulin production and, at the same time, a decrease in glucagon levels and insulin resistance.The review substantiates the feasibility of using GABA and drugs with a positive GABAeric effect in combination with new generation antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors in order to increase their antidiabetic potential.The search was carried out in the databases Pubmed, eLibrary, Medline. Keywords: diabetes mellitus, gamma-aminobutyric acid, glucagon-like peptide-1, GLP-1 receptor agonists, glucose-dependent insulinotropic peptide, dipeptidyl peptidase inhibitors, sodium-glucose cotransporter 2 inhibitors. The search was carried out from 2000 to 2022, but the review presents the results studies published mainly in the last 3 years, due to the requirements of the journal for the maximum amount of work and the number of sources.

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Section: общая характеристика ингибиторов нглт-2unclassified

Section: класс-специфические свойства препаратов ингибирующих нглт-2unclassified

Section: Introductionunclassified

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Synergistic effects of GABA and hypoglycemic drugs

Tyurenkov,

Faibisovich,

Bakulin

2023

Probl Endokrinol (Mosk)

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Long-term analysis of сanagliflozin budget impact in adult patients with type 2 diabetes mellitus and diabetic nephropathy in the Russian Federation

Avxentyev

Makarova

2022

Farmakoèkonomika

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Background. Diabetic nephropathy (DN) is a specific kidney lesion in patients with diabetes mellitus, which leads to the development of endstage kidney disease and requires substitutive renal therapy (dialysis or transplantation). Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, which exerts a renoprotective effect. According to the published data, the application of canagliflozin in patients with type 2 diabetes mellitus (DM2) and DN could postpone dialysis therapy for almost 13 years.Objective: to perform a long-term analysis of canagliflozin budget impact in adult patients with DM2 and DN from the point of view of the constituent entities of the Russian Federation.Material and methods. A group of comparison for canagliflozin was placebo (no renoprotective pharmacotherapy). The authors proposed a mathematical model for DN progression in groups of patients who received canagliflozin (100 mg orally, daily, long-term) or placebo. The model was based on the extrapolation of the CREDENCE study data. The model was used for the analysis of the direct costs on the lifetime pharmacotherapy and dialysis per one patient. Epidemiologic data from the federal register on the number of adult patients with DM and DN prevalence among these patients were used to evaluate the size of the target population. Based on the clinical recommendations and the medical care standards for patients with DM and the data on the actual state procurement of SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists in 2021, we evaluated the share of patients with DM2+DN who currently do not receive renoprotective therapy but who must be supplied with canagliflozin according to the standards. Among this population, we determined the patients with the glomerular filtration rate within 30–90 ml/min/1.73 m2, which provides the comparability of the target population with patients included in CREDENCE clinical study.Results. Direct medical costs per one patient receiving canagliflozin therapy were 678 108 rubles, which was 52.8% (759,239 rubles) lower than without renoprotective pharmacotherapy (1,437,347 rubles). As a result, considering the modeling period and current practice, the budget costs for pharmacotherapy of patients with DM2+DN were 99.82 billion rubles, in comparison with the proposed practice, which was 47.09 billion rubles (difference in budget costs is 52.73 billion rubles, or 52.8%). The accumulated costs of the regional health care system were lower in patients receiving canagliflozin in comparison with patients without renoprotective pharmacotherapy 11 years after the beginning of treatment.Conclusion. The expansion of canagliflozin application in the therapy for patients with DM2+DN leads to the budget cost cuts in the long run due to the extension of the dialysis-free period.

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Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Cited by 2 publications

References 40 publications

Synergistic effects of GABA and hypoglycemic drugs

Synergistic effects of GABA and hypoglycemic drugs

Long-term analysis of сanagliflozin budget impact in adult patients with type 2 diabetes mellitus and diabetic nephropathy in the Russian Federation

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