Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors

Wojcik, Cezary; Warden, Bruce A.

doi:10.1007/s11886-019-1219-4

Cited by 43 publications

(43 citation statements)

References 89 publications

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“…In addition, it is believed that through complex regulatory mechanisms associated with some of the processes mentioned above, SGLT2is may also have antiinflammatory and antioxidant effects. The combined effect of metabolic and haemodynamic factors on the slowing of the atherosclerotic process is also being taken into consideration [1,12,13,26,[57][58][59][60][61][62][63][64][65][66][67].…”

Section: The Postulated Mechanisms Of the Beneficial Effects Of Sglt2mentioning

confidence: 99%

Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

et al. 2020

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Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.

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Section: The Postulated Mechanisms Of the Beneficial Effects Of Sglt2mentioning

confidence: 99%

Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

et al. 2020

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“…SGLT2i entered the market in 2013 and were originally developed and approved for treatment of hyperglycemia in type 2 diabetes mellitus. [26] Cardiovascular benefits (including salient heart failure protection) were serendipitously discovered in response to guidance from the Food and Drug Administration (FDA) in 2008 requiring all new glucose-lowering therapies to prove cardiovascular safety before market approval. [27]…”

Section: Pharmacotherapymentioning

confidence: 99%

“…Though more work is needed to fully elucidate these mechanisms, several salient hypotheses have been proposed that include improvement in conventional cardiovascular risk factors (hyperglycemia, dyslipidemia, hypertension, and elevated body mass index [BMI]), improvement in hemodynamics, natriuretic effects, reduced cardiac and renal remodeling, inhibition of hormone dysregulation, use of more efficient metabolic substrates, ion channel inhibition, anti-inflammatory effects, and anti-oxidant effects. [26] …”

Section: Pharmacotherapymentioning

confidence: 99%

“…Although SGLT2i do not directly induce hypoglycemia, due to their insulin-independent mechanism of action with reduced glucosuria with lower blood glucose levels (ceasing somewhere ~40–80 mg/dL), the risk of hypoglycemia is increased primarily in combination with insulin or insulin secretagogues. [26] However, dose adjustments for insulin or insulin secretagogues are not routinely recommended when initiating SGLT2i owing to the increased risk for diabetic ketoacidosis (DKA). Among patients with well controlled HgbA1c levels at baseline, or known history of frequent hypoglycemic events, a dose reduction or discontinuation of insulin or insulin secretagogues is prudent.…”

Section: Pharmacotherapymentioning

confidence: 99%

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Optimizing sodium-glucose co-transporter 2 inhibitor use in patients with heart failure with reduced ejection fraction: A collaborative clinical practice statement

Warden

Steiner

Camacho

et al. 2021

American Journal of Preventive Cardiology

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Highlights HFrEF is a debilitating disease with substantial morbidity, mortality, and costs. SGLT2i reduce adverse cardiovascular (including HF) and renal events. SGLT2i have ushered in a new treatment paradigm for HFrEF management. Collaboration between preventive cardiology and heart failure will optimize HF care. Collaboration aims to optimize CV risk factors and SGLT2i access and adherence.

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“…Изучение эффективности иНГЛТ2 у пациентов с СН с и без СД2 стало возможными как после представления результатов оригинальных исследований по оценке их сердечно-сосудистой безопасности, так и после получения данных об их возможных механизмах действия [10,[23][24][25]. Потенциальные механизмы действия иНГЛТ2 многочисленны, глюкозонезависимы и выходят за рамки умеренного диуретического эффекта за счет натрийуреза (рис.…”

Section: эффективность дапаглифлозина при сн-нфв в зависимости от статуса углеводного обменаunclassified

Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

2020

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Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

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Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors

Cited by 43 publications

References 89 publications

Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

Optimizing sodium-glucose co-transporter 2 inhibitor use in patients with heart failure with reduced ejection fraction: A collaborative clinical practice statement

Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

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