Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Huang, Keming; Luo, Xianling; Liao, Bin; Li, Guang; Feng, Jian

doi:10.1186/s12933-023-01816-5

Cited by 37 publications

(15 citation statements)

References 222 publications

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“…The different SGLT2i subtypes also differ in terms of efficacy and indication. 41 Clinical studies have shown that empagliflozin and dapagliflozin are inconsistent, especially in terms of cardiovascular death. 42 The inconsistency in cardiovascular death between empagliflozin and dapagliflozin may be due to the intrinsic pharmacological difference.…”

Section: ■ Discussionmentioning

confidence: 99%

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome

Song,

Liu,

et al. 2024

ACS Pharmacol. Transl. Sci.

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The evidence for sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of type 2 diabetes or chronic heart failure was sufficient but lacking in acute coronary syndrome (ACS). Our aim was to investigate the effects of SGLT2i on cardiovascular outcomes in ACS patients. Studies of SGLT2i selection in ACS patients were searched and pooled. Outcomes included all-cause death, adverse cardiovascular events, cardiac remodeling as measured by the left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD), cardiac function as assessed by the left ventricular ejection fraction (LVEF) and NT-proBNP, and glycemic control. Twenty-four studies with 12,413 patients were identified. Compared to the group without SGLT2i, SGLT2i showed benefits in reducing all-cause death (OR 0.72, 95% CI [0.61, 0.85]), major adverse cardiovascular events (MACE) (OR 0.44, 95% CI [0.30, 0.64]), cardiovascular death (OR 0.66, 95% CI [0.54, 0.81]), heart failure (OR 0.52, 95% CI [0.44, 0.62]), myocardial infarction (OR 0.68, 95% CI [0.56, 0.83]), angina pectoris (OR 0.37, 95% CI [0.17, 0.78]), and stroke (OR 0.48, 95% CI [0.24, 0.96]). Results favored SGLT2i for LVEDD (MD −2.03, 95% CI [−3.29, −0.77]), LVEF (MD 3.22, 95% CI [1.71, 4.72]), and NT-proBNP (MD −171.53, 95% CI [−260.98, −82.08]). Thus, SGLT2i treatment reduces the risk of all-cause death and MACE and improves cardiac remodeling and function in ACS patients.

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Section: ■ Discussionmentioning

confidence: 99%

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome

Song,

Liu,

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…In recent years, sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors have demonstrated significant promise in the treatment of DCM. 39 , 40 , 41 , 42 , 43 , 44 , 45 Commonly used SGLT‐2 inhibitors include empagliflozin, dapagliflozin, and canagliflozin. 39 As opposed to conventional insulin‐dependent hypoglycemic medications, SGLT‐2 inhibitors work to lower blood glucose by inhibiting SGLT‐2R on the renal tubules, reducing glucose reabsorption from the tubules and increasing excretion, and to some extent inhibiting SGLT‐1R on the intestine, reducing glucose absorption and utilization in the small intestine to achieve hypoglycemic effects.…”

Section: Recent Advances In Treatment Researchmentioning

confidence: 99%

“… 39 , 40 , 41 , 42 , 43 , 44 , 45 Commonly used SGLT‐2 inhibitors include empagliflozin, dapagliflozin, and canagliflozin. 39 As opposed to conventional insulin‐dependent hypoglycemic medications, SGLT‐2 inhibitors work to lower blood glucose by inhibiting SGLT‐2R on the renal tubules, reducing glucose reabsorption from the tubules and increasing excretion, and to some extent inhibiting SGLT‐1R on the intestine, reducing glucose absorption and utilization in the small intestine to achieve hypoglycemic effects. 39 SGLT‐2 inhibitors enable higher urine glucose and sodium excretion, and decreased blood volume in a chronic hyperglycemic setting, lowering cardiac Preload and afterload and raising cardiac output.…”

Section: Recent Advances In Treatment Researchmentioning

confidence: 99%

Progress in the treatment of diabetic cardiomyopathy, a systematic review

Shou,

Li,

Fang

et al. 2024

Pharmacology Res & Perspec

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Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.

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“…Despite the remarkable consistency of the benefit of the SGLT‐2is on a range of outcomes in patients with HF, type 2 diabetes and CKD, there is still uncertainty as to how these drugs work in each setting. 20 , 21 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 Despite being developed as glucose‐lowering medications, they are effective in patients without type 2 diabetes with HF and kidney disease. It may be that different postulated mechanisms are more or less important in each disease.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Improving heart failure outcomes with sodium‐glucose cotransporter 2 inhibitors in different patient groups

Jhund

2023

Diabetes Obesity Metabolism

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Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) were originally developed for the treatment of hyperglycaemia in type 2 diabetes. Because of regulatory requirements to show the safety of this new class of drugs, a large randomized cardiovascular (CV) outcomes trial was completed but this showed that instead of having a neutral effect on heart failure (HF) outcomes, that these drugs could reduce HF outcomes in this population. Subsequent trials with SGLT-2is have shown that HF hospitalizations are reduced by 30% and CV death or HF hospitalization by 21% in patients with type 2 diabetes. These findings have extended to patients with HF with reduced and mildly reduced or preserved ejection fraction in whom further HF hospitalizations are reduced by 28% and CV death or HF hospitalizations reduced by 23%, and that it is becoming a central therapy for the treatment of HF. Moreover, the benefit in patients with HF is observed regardless of the presence or absence of type 2 diabetes. Similarly, in patients with chronic kidney disease and albuminuria, with and without type 2 diabetes, the benefit of SGLT-2is is clearly seen with a 44% reduction in HF hospitalization and 25% reduction in CV death or HF hospitalization.These trials support the use of SGLT-2is in improving HF outcomes in a broad range of patients, from those with type 2 diabetes, chronic kidney disease and those with pre-existing HF regardless of ejection fraction.

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Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Cited by 37 publications

References 222 publications

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome

Progress in the treatment of diabetic cardiomyopathy, a systematic review

Improving heart failure outcomes with sodium‐glucose cotransporter 2 inhibitors in different patient groups

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